concanavalin-a and Multiple-Sclerosis

Topics: Animals; Antigens; Cell Communication; Cell Count; Concanavalin A; Culture Media; DNA; Dose-Response Relationship, Immunologic; Humans; Lymphocyte Activation; Lymphocytes; Lymphokines; Macrophages; Mice; Multiple Sclerosis; Phytohemagglutinins; T-Lymphocytes; T-Lymphocytes, Regulatory; Time Factors

Parenterally administered human recombinant type I interferons (hrIFN) in relapsing-remitting multiple sclerosis (RRMS) decrease relapses and spontaneous in vitro IFN-gamma production, reduce clinical progression, and decrease magnetic resonance imaging (MRI)-defined disease activity and lesions. Parenterally administered type I IFN use is limited by clinical and chemical toxicities, and the induction of antibodies that abrogate their activity in vivo correlated with the loss of clinical benefit. Therefore, we determined whether ingested IFN-alpha was non-toxic and had biological effects in humans. Ingested hrIFN-alpha showed no toxicity in normal volunteers or patients with RRMS at doses ranging from 300 to 100,000 units. In subjects with RRMS, a significant decrease in Con A-mediated proliferation and serum soluble intercellular adhesion molecule-1 (sICAM-1), a surrogate measure for disease activity in MS, was found after ingesting 10,000 and 30,000 units IFN-alpha The RRMS subjects also showed decreased IL-2 secretion after ingesting 10,000 units IFN-alpha and decreased IFN-gamma, TGF-beta and IL-10 production after ingesting 30,000 units IFN-alpha. The decreased secretion of IFN-gamma and IL-2 by ingested IFN-alpha suggests that oral IFN-alpha may cause a functional inhibition of Th J-like T helper cells in RRMS, a potential site of intervention at the level of effector T cells in MS. Our studies support the oral use of human IFN-alpha as a biological response modifier in humans.

Topics: Administration, Oral; Cell Division; Concanavalin A; Humans; Inflammation Mediators; Intercellular Adhesion Molecule-1; Interferon-alpha; Monocytes; Multiple Sclerosis; Recombinant Proteins; Treatment Outcome

Multiple sclerosis (MS) is presumed to be a T-cell mediated chronic inflammatory disease of the central nervous system. We have previously reported that IFN-beta 1b (Betaseron) decreases CD3-mediated TNF-alpha secretion but increases another inflammatory cytokine, IL-6 after three months of treatment. We have now examined cytokine secretion of peripheral blood mononuclear (PMNC) cells after stimulation with OKT3 (anti-CD3) monoclonal antibody (mAb) or Con A in subjects with clinically stable relapsing MS before and three, six and nine months after initiating IFN-beta 1b treatment. At nine months Con A-induced TNF-alpha secretion decreased significantly below baseline but IFN-gamma secretion increased above baseline. There were no significant changes in Con A-induced IL-4 over the six month period and no changes in IL-10 and IL-2 over the nine month period. After nine months on treatment the CD3-induced TNF-alpha and IFN-gamma secretion was not significantly different from the original baseline values. Increased CD3-mediated IL-6 secretion in on-treatment compared to pre-treatment samples at three months gradually declined to baseline values by nine months on-treatment. There was no significant changes from baseline compared to nine months on-treatment in CD3-mediated IL-2, IL-4, IL-10. IFN-beta 1b (Betaseron) treatment has no clear persistent effect on CD3-induced inflammatory or counterregulatory anti-inflammatory cytokine secretion.

Topics: Adult; CD3 Complex; Concanavalin A; Cytokines; Female; Humans; Injections, Subcutaneous; Interferon-beta; Interferon-gamma; Interleukins; Male; Multiple Sclerosis; Recurrence; Tumor Necrosis Factor-alpha

Plasma acute-phase proteins (APPs) glyco-isoforms are important biomarkers of inflammatory processes such as those occurring in multiple sclerosis (MS). Specific analysis of these proteins is often hampered by sample biochemical complexity. The aim of our study was to set up a method to accurately visualize, identify and quantify APPs glyco-isoforms in human serum. An enrichment strategy based on affinity chromatography using the carbohydrate-binding proteins concanavalin A (ConA) and erythrina cristagalli lectin (ECL) was applied to pooled serum samples from 15 patients and 9 healthy individuals. Image analysis of 2-DE detected 30 spots with a fold change higher than 1.5. A total of 14 were statistically significant (p value<0.05): 7 up-regulated and 7 down-regulated in MS samples. ESI LC-Nanospray IT mass spectrometry analysis confirmed that all of them were APPs isoforms supporting the idea that the accurate analysis of differential glycosylation profiles in these biomarkers is instrumental to distinguish between MS patients and healthy subjects. Additionally, overlaps in ConA/ECL maps protein patterns suggest how the used lectins are able to bind sugars harbored by the same oligosaccharide structure. Among identified proteins, the presence of complex and/or hybrid type N-linked sugar structures is well known. Performing galectin-3 binding and Western blotting, we were able to demonstrate a correlation between hybrid type glyco-isoforms of β-haptoglobin and MS. In conclusion, although the patho-physiological role of the identified species still remains unclear and further validations are needed, these findings may have a relevant impact on disease-specific marker identification approaches.

Topics: Acute-Phase Proteins; Adult; Blotting, Western; Concanavalin A; Electrophoresis, Gel, Two-Dimensional; Female; Galectin 3; Glycoproteins; Humans; Image Processing, Computer-Assisted; Lectins; Male; Middle Aged; Multiple Sclerosis; Plant Lectins; Protein Isoforms; Proteomics; Reproducibility of Results; Serum; Spectrometry, Mass, Electrospray Ionization

T cells responsive to T-cell receptor (TCR) determinants may regulate pathogenic Th1 responses in patients with multiple sclerosis (MS) through interleukin (IL)-10-dependent bystander suppression. In this study, innate IL-10- and interferon (IFN)-gamma-secreting T cells responsive to TCR peptides were quantified in peripheral blood mononuclear cells of MS patients and healthy controls (HC) using the ELISPOT assay. Most HC had vigorous IL-10 but low IFN-gamma frequencies to BV5S2 and BV6S1 peptides. In contrast, MS patients had significantly lower IL-10 frequency responses to the TCR peptides but normal responses to concanavalin A. Patients undergoing TCR-peptide vaccination had moderate responses that fluctuated in concert with vaccination. In an MS patient and HC, expression of BV6S1 by activated memory T cells was inversely associated with the presence of IL-10-secreting BV6S1-reactive T cells. These results suggest that MS patients have diminished frequencies of innate TCR-reactive T cells that may allow oligoclonal expansion of activated autoreactive Th1 effector cells expressing cognate V genes.

Topics: Adult; Aged; Amino Acid Sequence; Concanavalin A; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression Regulation; Humans; Immunologic Memory; Interferon-gamma; Interleukin-10; Lymphocyte Activation; Male; Middle Aged; Molecular Sequence Data; Multiple Sclerosis; Peptide Fragments; Receptors, Antigen, T-Cell, alpha-beta; T-Lymphocyte Subsets; Th1 Cells; Vaccination

Changes of glycosylation of cerebrospinal fluid proteins such as alpha2-macroglobulin, and prostaglandin D synthase were studied by lectin blotting, using concanavalinA, in multiple sclerosis (n = 42) and neuropathies (n = 20) in comparison to neurological controls (n = 22). The concanavalinA-reactivity of alpha2-macroglobulin, which was increased in the neuropathies but not in multiple sclerosis compared to controls, correlated with the total concanavalinA-reactivity in controls and neuropathies but not in multiple sclerosis, indicating that the protein could be abnormally glycosylated in the latter disease. Although the concentration and the concanavalinA-reactivity of prostaglandin D synthase were not significantly different in the three groups, the two parameters correlated only in neuropathies but not in controls or multiple sclerosis, probably due to the high heterogeneity of the protein. These changes deserve to be studied in further detail in view of their potential clinical applications.

Topics: alpha 1-Antitrypsin; alpha-Macroglobulins; Blood Proteins; Cerebrospinal Fluid Proteins; Concanavalin A; Enzyme-Linked Immunosorbent Assay; Glycosylation; Hereditary Sensory and Motor Neuropathy; Humans; Intramolecular Oxidoreductases; Lipocalins; Molecular Probes; Multiple Sclerosis

The mechanism of action of recombinant IFNbeta1b (IFNbeta-1b), as a therapy for multiple sclerosis (MS), is still unknown but may result from the enhancement of ConA-induced suppressor cell function and the inhibition of IFNgamma secretion by lymphocytes. We previously demonstrated that IFNbeta-1b stimulated modest amounts of IL-10 secretion by monocytes and IL-10 activity, as cytokine synthesis inhibitory factor, was normal in MS. To determine whether IL-10 plays a role in IFNbeta-1b modulation of immune function in MS, we studied ConA-induced suppressor cell function and IFNgamma production in presence of IFNbeta-1b and an anti-IL-10 monoclonal antibody (mAb). Anti-IL-10 mAb significantly reduced the effect of IFNbeta-1b on ConA-induced suppressor cell function and IFNgamma production in healthy subjects; MS patients showed a trend of inhibition. We hypothesized that IL-10 may play a role in mediating the effects of IFNbeta-1b on suppressor cell function and IFNgamma production but suppressor molecules other than IL-10 could be also involved.

Topics: Adult; Antibodies, Monoclonal; Autoimmune Diseases; Cells, Cultured; Concanavalin A; Drug Interactions; Female; Humans; Immunologic Factors; Interferon beta-1a; Interferon beta-1b; Interferon-beta; Interleukin-10; Lymphocyte Activation; Male; Multiple Sclerosis; Recombinant Fusion Proteins; T-Lymphocytes, Regulatory

MS is presumed to be a T-cell-mediated chronic inflammatory disease of the CNS. We examined proliferation and cytokine secretion of mononuclear cells after stimulation with OKT3 [anti-CD3] monoclonal antibody (MAb) or concanavalin A (Con A) in subjects with stable relapsing-remitting MS (RR MS) before and after initiating interferon (IFN)-beta 1b treatment. There was no significant difference in pretreatment to on-treatment anti-CD3 mAb or Con A-induced proliferation in RR MS patients. There was significantly increased Con A-induced secretion of tumor necrosis factor (TNF)-alpha, IFN-gamma, interleukin (IL)-2, IL-6, and IL-10 and decreased IL-4 secretion in on-treatment compared with pretreatment peripheral blood mononuclear cell samples. However, on-treatment CD3-mediated secretion of TNF-alpha was significantly decreased, and IL-6 secretion was significantly increased compared with pretreatment values. IFN-gamma was also decreased in on-treatment cultures stimulated with anti-CD3 MAb, but these values did not reach statistical significance. Systemic side effects from IFN-beta 1b were associated with increased IL-6 secretion. There were no significant changes in CD3-mediated IL-4, IL-10, transforming growth factor (TGF)-beta, or IL-2 secretion or Con A-induced TGF-beta secretion. IFN-beta 1b (Betaseron) decreases CD3-mediated TNF-alpha secretion but increases another inflammatory cytokine, IL-6, that could potentially counteract its beneficial immunomodulatory effects.

Topics: Autoimmune Diseases; Concanavalin A; Humans; Immunologic Factors; Interferon beta-1a; Interferon beta-1b; Interferon-beta; Interferon-gamma; Interleukin-10; Interleukin-2; Interleukin-4; Interleukin-6; Lymphocyte Activation; Multiple Sclerosis; Muromonab-CD3; Recombinant Proteins; T-Lymphocytes, Cytotoxic; Tumor Necrosis Factor-alpha

Interferon-consensus 1 (IFN-Con 1) is a novel synthetic protein generated from codons for the most frequent amino acids in different type 1 IFNs. Compared with natural IFNs, IFN-Con 1 has been shown to have higher specific activity and antiproliferative activity and a higher ability to induce natural killer cells. In this study, the effects of IFN-Con 1 were compared with those of IFN-beta 1b and IFN-alpha 2a on HLA expression and lymphoproliferation. Human umbilical vein endothelial cells (HUVEC) express HLA class I but not class II molecules; however, both class I and class II molecules can be upregulated by IFN-gamma. IFN-Con-1 shared with IFN-beta 1b and IFN-alpha 2a the capacity to enhance HLA class I expression on HUVEC, alone and in combination with IFN-gamma. Although IFN-Con 1 had no effect on the basal expression of HLA class II molecules, it inhibited the IFN-gamma-induced class II expression on the HUVEC in a dose-dependent fashion. When this effect was compared among the three IFNs on mass basis, IFN-Con 1 activity was intermediate between that of IFN-beta 1b and IFN-alpha 2a. IFN-Con 1 also demonstrated an inhibitory effect on mitogen-driven lymphoproliferation similar to that of IFN-alpha 2a and exceeded that of IFN-beta 1b. The results indicate that IFN-Con 1 has immunomodulatory effects similar to those of IFN-beta 1b and IFN-alpha 2a, which could be relevant to the treatment of autoimmune and virus-mediated diseases.

Topics: Adjuvants, Immunologic; Cell Line; Concanavalin A; Drug Evaluation, Preclinical; Histocompatibility Antigens Class II; Humans; Interferon alpha-2; Interferon beta-1a; Interferon beta-1b; Interferon Type I; Interferon-alpha; Interferon-beta; Lymphoproliferative Disorders; Multiple Sclerosis; Recombinant Proteins; RNA, Messenger

Chronic relapsing experimental allergic encephalomyelitis (CR.EAE) was induced by immunizing Lewis rats with total guinea-pig spinal cord (GPSC) tissue emulsified in enriched complete Freund's adjuvant (CFA). The proliferative responses of draining inguinal and popliteal lymph node cells to GP.MBP, purified protein derivative (PPD) and concanavalin A (ConA) appeared significantly modulated according to the clinical state of the animals. Responses appeared significantly decreased in both lymphoid compartments during the recovery periods compared with that during relapses. Therapeutic treatment of CR.EAE with cyclosporin and different lysolecithin derivatives, such as ET-18-OCH3, SRI 62-843 and MLS 266-337, starting at the spontaneous remission of the first disease bout, could suppress the manifestation of further relapses. Whereas cyclosporin only delayed the onset of the disease relapse until discontinuation of treatment, all lysolecithins showed a curative effect in most animals. Plasma corticosterone levels measured at different time points in placebo, cyclosporin and MLS 266-377-treated rats showed a strong correlation with the clinical state of the animals. High corticosterone levels were detected during stages of acute paralysis, whereas a decrease to normal levels was noted during each recovery phase.

Topics: Animals; Autoimmune Diseases; Concanavalin A; Corticosterone; Cyclosporine; Dexamethasone; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Female; Furans; Guinea Pigs; Lymph Nodes; Lymphocyte Activation; Lysophosphatidylcholines; Multiple Sclerosis; Myelin Basic Protein; Phospholipid Ethers; Rats; Rats, Inbred Lew; Tuberculin

Interferons are biological molecules with antiviral, antiproliferative, and immunomodulatory actions. Interferon alpha (IFN-alpha) and -beta are potentially useful in the treatment of multiple sclerosis (MS). IFN-gamma, in contrast, increases the frequency of exacerbations of MS. In this study, we compared the effect of recombinant human IFN-alpha, -beta, and -gamma on suppressor function in patients with MS. Nonspecific suppressor cell function, measured in a concanavalin A suppressor assay, was significantly decreased in 16 patients with progressive MS (mean percent suppression +/- SEM, 14.4 +/- 5.5 in patients with MS, 33.5 +/- 4.8 in 16 normal subjects; p less than 0.001). Recombinant human IFN-beta augmented suppressor function in MS to 45.4 +/- 5.1% (p less than 0.001) and in control subjects to 56.8 +/- 3.8% (p less than 0.001). Similarly, recombinant human IFN-alpha improved suppression in MS to 43.0 +/- 5.6% (p less than 0.001) and in control subjects to 51.1 +/- 5.9% (p less than 0.001). In contrast, recombinant human IFN-gamma had no effect on suppressor function in patients with MS and in control subjects. This study shows that IFN-alpha and -beta augment deficient suppressor function in MS, whereas IFN-gamma has no effect on suppressor function in the progressive phase of the disease.

Topics: Adult; Concanavalin A; Humans; Immune Tolerance; Immunologic Factors; Interferon-gamma; Interferons; Lymphocyte Activation; Middle Aged; Multiple Sclerosis; Recombinant Proteins; Stimulation, Chemical; T-Lymphocytes, Regulatory

In view of the immunoregulatory and antiviral properties of the interferons (IFNs), the production of and response to these cytokines in vivo and in vitro were assessed in 42 patients with multiple sclerosis (MS), a disease with features of autoimmunity and a viral infection. Serum IFN, determined by bioassay of antiviral activity at 10 intervals over 18 months, was detectable at levels ranging from 16 to 250 IU/ml, at least once and up to five times in 37 of the 42 patients. Of 420 samples tested, 88 (21%) were positive. None of the 71 serum samples from 37 healthy subjects contained detectable IFN activity. Neutralization of antiviral activity by antibodies showed that the serum IFN type was IFN-alpha in 82 samples, IFN-gamma only in 2, and both IFN-alpha and IFN-gamma were present in 4. At the initial time point the activity of 2'-5' oligoadenylate synthetase (OAS), an IFN-induced enzyme, was elevated in peripheral blood leucocytes (PBL) from 13 patients, but not in 7 patients seropositive for IFN, indicating that in some patients there was a failure of PBL to respond to endogenous IFN. In most patients the capacity of PBL in vitro to produce IFNs-alpha/beta or -gamma after induction by virus or mitogens, respectively, was likewise reduced. These various abnormalities in IFN responses could not be correlated with clinical assessments of disease activity but may reflect subclinical attacks. The abnormalities described, in particular the intermittent interferonemia in MS, are more striking than in other diseases previously reported, indicating an unusual component to the stimulus for IFN production (viral or other) or the response to it. The effects of endogenous IFN production may have implications for the scheduling of therapy with IFN in MS.

Topics: 2',5'-Oligoadenylate Synthetase; Adult; Cell Transformation, Viral; Concanavalin A; Enzyme Induction; Female; Humans; Interferon Type I; Interferons; Leukocytes; Longitudinal Studies; Lymphocyte Activation; Male; Middle Aged; Multiple Sclerosis; Parainfluenza Virus 1, Human

The extent to which symptomatic improvement in patients with multiple sclerosis treated with intravenous methylprednisolone depends on immunological actions of corticosteroids is unknown. In this study the effect of methylprednisolone on circulating T and B cell function has been assessed in vitro and in vivo. Low molar concentrations of methylprednisolone increased pokeweed mitogen-stimulated IgG synthesis by unfractionated lymphocytes in 20 patients with multiple sclerosis and 15 controls. Treatment with methylprednisolone was associated with increased IgG synthesis in a further cohort of 26 affected individuals although dose responsiveness to methylprednisolone was uninfluenced in these patients. Sequential concanavalin A-pokeweed mitogen-induced IgG synthesis by mononuclear cells was also stimulated by methylprednisolone. Phenotypic analysis of paired samples from 12 patients with multiple sclerosis, taken before and after treatment showed no alteration in CD4 or CD8 cells, their suppressor inducer or suppressor subpopulations or activated lymphocytes.

Topics: CD4-Positive T-Lymphocytes; Cells, Cultured; Concanavalin A; Female; Humans; Immunoglobulin G; Leukocyte Count; Lymphocytes; Male; Methylprednisolone; Middle Aged; Multiple Sclerosis; Phenotype; Pokeweed Mitogens; Reference Values; T-Lymphocytes, Regulatory

Topics: Concanavalin A; Humans; Immunoglobulin G; Magnetic Resonance Imaging; Multiple Sclerosis; Prospective Studies; T-Lymphocytes, Regulatory; Time Factors

We have serially studied immunoglobulin G secretion in vitro, natural killer cell function, and concanavalin A-induced suppression in a group of seven patients with relapsing-remitting multiple sclerosis. In two patients, the development of a large clinically asymptomatic MRI lesion was accompanied by reductions in natural killer cell function, immunoglobulin G secretion in vitro (after pokeweed mitogen stimulation), and concanavalin A-induced suppression without parallel change in lymphocyte markers. We did not see this type of change in matched controls nor in stable multiple sclerosis studied serially. When clinical attacks appeared, there was no significant change in immune function. We conclude that changes in immune function correlate well with the activity of the disease as recognized by MRI. We suspect that decreased natural killer cell function, immunoglobulin G secretion in vitro, and concanavalin A-induced suppression are secondary to the large lesions recognized by MRI.

Topics: Adult; Brain; Concanavalin A; Female; Humans; Immunoglobulin G; Killer Cells, Natural; Magnetic Resonance Imaging; Male; Multiple Sclerosis; Spinal Cord

Pokeweed-mitogen-induced IgG secretion, Con A suppression and T cell surface markers were measured in 30 chronic progressive multiple sclerosis (MS) patients and 21 healthy controls. Mean IgG secretion was higher in the MS patients than in the controls (2392 +/- 270 vs 1499 +/- 243); Con A suppression was lower (4 +/- 5% vs 24 +/- 4%) and the CD4/CD8 ratio was higher (4.1 +/- 0.4 vs 2.9 +/- 0.4). The above assays were used in vitro to monitor the effects of Wellferon (lymphoblastoid interferon) injections on this group of MS patients. Before treatment the INF-group (n = 14) did not differ from the PLA-group (n = 16). After 1 week of daily injections the level of IgG secreted was dramatically reduced in the INF group (629 +/- 96 ng/ml) compared to the PLA-group (1756 +/- 319 ng/ml). There was no change in either Con A suppression or T cell surface markers. IgG secretion remained lower in the INF-group for the 6 month treatment period. Following cessation of the injections and a 6 month washout period, IgG secretion in the INF-group rose and was equivalent to that observed in the PLA-group. A series of lymphocyte subset mixing experiments implicates the B lymphocyte subset as being directly affected by interferon injections in vitro.

Topics: Concanavalin A; Humans; Immunoglobulin G; In Vitro Techniques; Interferon Type I; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphocytes; Multiple Sclerosis; Pokeweed Mitogens

Interleukin-2 (IL-2) production by CD4-enriched T cells from multiple sclerosis (MS) patients and normal individuals stimulated with concanavalin A (conA) and/or autologous and allogeneic B lymphoid cell lines (B-LCL) was evaluated 24, 48 and 96 h after stimulation. ConA-stimulated CD4+ cells from MS patients did not produce significantly more IL-2 than normal CD4+ cells. In contrast, autologous B-LCL-induced IL-2 production by MS CD4+ cells significantly (P = 0.026) exceeded that produced by normal CD4+ cells identically stimulated after 24 h in culture. Differences in IL-2 production by CD4+ cells from MS patients reached highest significance using allogeneic B-LCL, whose stimulatory capacity was similar, whether established from normal individuals or MS patients. This increased IL-2 production in response to B-LCL may represent a supranormal response of CD4+ cells from MS patients to class II major histocompatibility (MHC)-associated stimuli. It suggests that the deficiency of suppressor T cell functions postulated to play a role in MS does not arise from a lack of IL-2 induction and might indicate that bursts of IL-2 production could play a role in MS.

Topics: Adult; Cells, Cultured; Concanavalin A; Humans; Interleukin-2; Lymphocyte Activation; Multiple Sclerosis; T-Lymphocytes; T-Lymphocytes, Cytotoxic

In vitro lymphocyte proliferation in response to allogeneic pooled cells, phytohaemaglutinin (PHA), and pokeweed mitogen (PWM), was measured in relation to HLA A, B and C status in 67 patients with clinically definite multiple sclerosis and in 67 age- and sex-matched controls. Analysis of covariance taking age into account showed significant effects only for A9 and B12 in controls and B27 and Cw3 in patients, fewer than would be expected by chance. It is concluded that HLA Class 1 status is not an important factor in regulating mitogen responsiveness.

Topics: Concanavalin A; HLA Antigens; Humans; Lymphocyte Activation; Multiple Sclerosis; Phytohemagglutinins; Pokeweed Mitogens

Concanavalin A (Con A)-induced suppressor activity has previously been shown to be reduced in multiple sclerosis (MS) patients with active clinical disease. In this study, we demonstrate that OKT3, as well as Con A induced suppressor activity mediated by unfractionated peripheral blood mononuclear cells is reduced in patients with the progressive form of MS. By performing reconstitution experiments involving E+, T4+, or T8+ cells derived from either MS patients or controls, and normal allogeneic macrophages or E- cells, we sought to define the cellular basis for this suppressor defect. In both MS and control groups, E+ cells were required to obtain measurable levels of suppression. Suppressor levels induced by Con A-activated cultures containing E+ cells from MS patients were lower than those induced by those containing control donor E+ cells. Suppression mediated by T8+ cells from MS patients was also lower than for controls. In the control group, suppression mediated by T8+ cells exceeded that mediated by T4+ cells; such differences were not apparent in the MS group. These results suggest that although Con A-induced suppression can be mediated by a number of T and non-T cell subsets, the functional suppressor defect measured in the MS population does involve the T8+ cell subset.

Topics: Adult; Antibodies, Monoclonal; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; Cell Separation; Concanavalin A; Humans; Leukocyte Count; Lymphocyte Activation; Middle Aged; Multiple Sclerosis; Phenotype; T-Lymphocytes, Regulatory

Patients with progressive multiple sclerosis (MS) demonstrated persistent reductions in levels of concanavalin A (Con A)-induced suppressor activity and heightened levels of in vitro pokeweed mitogen (PWM)-induced IgG secretion. The reduced Con A suppressor activity could not be reversed by addition of interleukin 2 (IL-2). Cyclosporine A (CsA) treatment did not alter the defect in Con A-induced suppressor activity, but did markedly inhibit T8+ cell-mediated alloantigen directed cytolytic activity; this latter defect was reversible by in vitro addition of IL-2. CsA-treated patients did not differ from placebo-treated patients with regard to levels of PWM-induced IgG secretion or proliferative responses of their mononuclear cells to Con A. The results indicate that CsA treatment of MS patients reduces cytolytic function from baseline normal values, but does not alter aberrant suppressor cell function.

Topics: Adult; Concanavalin A; Cyclosporins; Cytotoxicity, Immunologic; Humans; Immunoglobulin G; Interleukin-2; Isoantigens; Middle Aged; Multiple Sclerosis; Pokeweed Mitogens; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Regulatory

In vitro lymphocyte proliferation in response to allogeneic pooled cells, mitogens (PHA, Con A and PWM), and PPD was measured in 67 patients with clinically definite MS and in 67 age and sex-matched controls. Overall, dose-response curves in the two groups were similar, but response to PHA and PWM was significantly greater among patients, and a greater percentage of patients failed to respond to peak and suboptimal PPD concentrations. There was a reduced response to allogeneic pooled cells in Dw2 positive controls, and, in both patients and controls, a tendency towards a higher PPD response in Dw2 positive males. The results suggest that there is some alteration of balance of immune regulation in MS, which is slightly affected by Dw2 status.

Topics: Adolescent; Adult; Aged; Concanavalin A; Female; Humans; Immunity, Cellular; Lymphocyte Activation; Male; Middle Aged; Multiple Sclerosis; Phytohemagglutinins; Pokeweed Mitogens; Stimulation, Chemical; Tuberculin

Supernatants of peripheral blood lymphocytes (PBL), containing lymphokines, isolated from MS patients and healthy subjects were tested for demyelinating activity in organotypic culture of the rat cerebellum. PBL were isolated on Ficoll-paque gradient and cultures in RPMI 1640 medium for 72 h with or without phytohemagglutinin and Concanavalin A. Both stimulated and unstimulated PBL supernatants from MS patients consistently demyelinated cerebellum cultures. The supernatants of unstimulated PBL from healthy subjects did not produce demyelination, however, slight effect was present in the cultures treated with PBL stimulated supernatants. The results indicate that lymphokines might be involved in demyelination in MS.

Topics: Adult; Animals; Concanavalin A; Culture Techniques; Demyelinating Diseases; Humans; Lymphocytes; Lymphokines; Middle Aged; Multiple Sclerosis; Phytohemagglutinins; Rats; Rats, Inbred Strains

Peripheral blood leucocyte (PBL) cultures of patients with meningoencephalitis, myasthenia gravis, Alzheimer's dementia, Huntington's chorea as well as patients who were recovering from cerebrovascular accidents or from craniotomy for brain tumours, all had defective interferon-gamma (IFN-gamma) responses to stimulation with concanavalin A (Con A) and phytohaemagglutinin (PHA), similar to those already described for PBL cultures of patients with multiple sclerosis. Specifically, cultures from a significant percentage of the patients failed to produce IFN after stimulation with either of the two mitogens. The yields from those cultures that did respond were not significantly lower than those from cultures of healthy blood donors. With increased doses of Con A, the cerebrovascular accident, meningo-encephalitis and MS groups kept their low response frequencies, while the other groups, i.e., myasthenia gravis, Alzheimer's dementia, Huntington's chorea and post-craniotomy, developed an increased response frequency. A good concordance was found between responsiveness to Con A and PHA. With pokeweed mitogen (PWM) as an inducer, no reduction in response frequencies or IFN yields were seen in any of the patient groups. Also, in general, yields were higher with PWM than with Con A.

Topics: Cells, Cultured; Concanavalin A; Humans; Interferon Inducers; Interferon-gamma; Leukocytes; Multiple Sclerosis; Nervous System Diseases; Phytohemagglutinins; Pokeweed Mitogens

The production of gamma interferon (IFN) by mononuclear cells (MNC) from patients with exacerbating/remitting multiple sclerosis (MS) and controls was evaluated. After 3 days of culture with concanavalin A, the amount of gamma IFN in supernatant fluids was determined by radioimmunoassay. MNC from MS patients produced significantly (P less than 0.001) more gamma IFN than MNC from either normal controls or patients with other neurologic diseases. Levels of gamma IFN in the serum and CSF were also measured. Despite the relative absence of gamma IFN in serum (4 positive of 30), all CSF samples tested had low, but detectable, levels of gamma IFN (0.3 to 1.4 U/ml). These studies suggest that some of the autoimmune features and immunologic abnormalities in MS may be related to elevated gamma IFN production.

Topics: Adult; Concanavalin A; Humans; In Vitro Techniques; Interferon-gamma; Killer Cells, Natural; Lymphocytes; Middle Aged; Multiple Sclerosis

Peripheral blood leucocytes from multiple sclerosis (MS) patients and from normal individuals were tested for their interferon (IFN) producing capacity after stimulation in vitro with various lectins and viruses. The lectins, Con A, PHA and PWM, induced IFN-gamma. In a kinetic study, the response to Con A revealed itself as an all or none event: the number of responding cultures increased with increasing mitogen dose, but the IFN yield in responding cultures did not differ significantly between dose levels. Thus, any patient or donor could easily be rated as a responder or non-responder. About 1/2 of the MS patients were found to be non-responders if Con A or PHA were used as stimuli. Ninety per cent of the normal donors on the other hand were responders. With PWM as a stimulus 100% of both the MS patients and normal donor groups were found to be responders. Also, with PWM very small doses were sufficient to obtain a 100% response rate among tested cultures, and IFN production persisted for 5 days, while with Con A or PHA it was arrested after 2-3 days. The results indicate that the MS associated lesion is not the absence of functional impairment of all IFN-gamma producing cells, but in only a fraction of them or in an accessory cell population required for the response to Con A and PHA but not to PWM. Newcastle disease virus (NDV) and vesicular stomatitis virus (VSV) both induced IFN-alpha. With NDV as the inducer response rates were 100% and yields were high irrespective of whether the cells were derived from patients or control donors. In contrast, with VSV as the inducer lower response rates were found in cultures from MS patients than in those from controls.

Topics: Adult; Concanavalin A; Dose-Response Relationship, Immunologic; Humans; Interferons; Leukocytes; Middle Aged; Multiple Sclerosis; Newcastle disease virus; Phytohemagglutinins; Pokeweed Mitogens; Vesicular stomatitis Indiana virus

The relative proportions as well as cell surface and functional properties of T suppressor (T8+) and T helper (T4+) cells in peripheral blood mononuclear cells ( MNCs ) of MS patients were analyzed. The proportion of T8 cells compared to normal controls was suggestively lower in patients during relapses and significantly lower in those with progressive disease. The density of T8+ antigen on cells of MS patients with active disease as measured by median fluorescence intensity ( MFI ) was also decreased compared to controls and stable MS patients. Using OKT8-mAb modulated MNCs as a model, we found that reduction of T8 antigen density results in substantial discrepancies between FACS and microscope methods for enumeration of T8+ cells. Levels of pokeweed mitogen-induced IgG secretion by MNCs of MS patients did not correlate with proportion of T8+ cells within the MNCs , but rather with the functional activity of the T8+ cells of given individuals, as tested in an in vitro suppressor assay using constant numbers of T8+ cells.

Topics: Adult; Antigens, Surface; Concanavalin A; Humans; Immunoglobulin G; Mitomycin; Mitomycins; Monocytes; Multiple Sclerosis; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Pokeweed mitogen (PWM)-driven immunoglobulin synthesis (IgG, IgA, IgM) and concanavalin A (Con A)-stimulated suppression of allogeneic mixed leukocyte reaction (MLR) were studied and compared to T-cell subsets defined by monoclonal antibodies OKT4 and OKT8 in patients with multiple sclerosis (MS). The group of patients with active progressive MS showed diminished suppressor activity as measured by T-cell functional tests and also an elevated OKT4/OKT8 ratio. The group of MS patients in remission did not show these abnormalities. However, this correlation between functional tests and T-cell phenotypes was not found when separate individuals were considered within the subgroups of MS. Since neither OKT4 nor OKT8-reactive cells represent homogeneous functional subsets of T cells, the OKT4/OKT8 ratio does not account for the functional immunological status of separate individuals but rather provides a global evaluation of T-cell subset disturbances in different groups of diseases.

Topics: Adult; Aged; Antigens, Surface; Concanavalin A; Female; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Lymphocyte Culture Test, Mixed; Male; Middle Aged; Multiple Sclerosis; Phenotype; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Peripheral blood leukocyte (PBL) cultures from only 37% of MS patients produced detectable HuIFN-gamma in response to ConA as opposed to 85% of the cultures derived from normal blood donors. However, the yields in patient-derived cultures that were responsive, were not lower than those in cultures from controls. Production of HuIFN-alpha after stimulation with Sendai virus was not aberrant in cells taken from MS patients. The difference in HuIFN-gamma response rate between MS and normal donor-derived cells was more pronounced when DR2+ carriers were compared amongst each other than when DR2-k carriers were compared. Among the MS patients, the failure of PBLs to produce HuIFN-gamma in response to ConA was not correlated with age, sex, disease duration and type of disease. However, positive correlations were found with current disability indices and past disease progression rates. Unstimulated NK-activities of MS patient-derived PBLs were not different from those of normal donor-derived cells. the degree of augmentation of the activity by stimulation with ConA and interferon-alpha was also normal. Within the MS patients group, but not in the control group, there was a trend for DR2+ carriers to have lower spontaneous and stimulated NK-activities than DR2- individuals.

Topics: Adult; Cells, Cultured; Concanavalin A; Female; Histocompatibility Antigens Class II; HLA-DR Antigens; Humans; Interferons; Killer Cells, Natural; Leukocytes; Male; Multiple Sclerosis; Parainfluenza Virus 1, Human; Phenotype

Peripheral blood lymphocytes from patients with multiple sclerosis (MS) and two control groups, patients with neurologic diseases other than MS and healthy individuals, were examined for their cellular response to basic protein (BP), suppressor cell activity elicited by concanavalin A (ConA) and enumeration of T gamma cells. Lymphocytes from patients with active and chronic progressive MS showed the highest blastogenic stimulation in response to BP, the lowest ConA-induced suppression and the lowest absolute and relative number of T gamma cells. Lymphocytes from patients with nonactive or slowly progressive MS showed BP blastogenic stimulation similar to or slightly higher than that of the control groups. The ConA suppressor activity and the absolute and relative number of T gamma cells in the nonactive MS group were within normal ranges. The results indicate that although hypersensitivity to BP may be accompanied by deficient immunoregulatory activity, there is no pattern in the sequence of events. In addition, in some instances, changes in the immunoregulatory cells occurred with little or no effect on the cellular response to the neural antigen.

Topics: Adrenocorticotropic Hormone; Adult; Concanavalin A; Female; Humans; Immunity, Cellular; Leukocyte Count; Lymphocyte Activation; Male; Middle Aged; Multiple Sclerosis; Myelin Basic Protein; T-Lymphocytes, Regulatory

In vitro immune function was assessed in patients with multiple sclerosis (MS) who were receiving Imuran therapy, in untreated MS patients, and in controls. In untreated stable MS patients, concanavalin A (Con A)-driven mitogenic reactivity (T effector function) and Con A-induced suppressor activity were modestly reduced compared to controls; pokeweed mitogen-induced immunoglobulin G (IgG) secretion was increased. Untreated patients with active MS demonstrated high levels of IgG secretion and marked decreases in suppressor activity. In Imuran-treated patients, Con A mitogenic responses and suppressor activity were comparable to those observed in untreated stable patients, and IgG secretion was reduced. The results in the treated patients likely reflect a direct effect of Imuran on B cell function rather than an indirect effect mediated via suppressor cells.

Topics: Adolescent; Adult; Antibody Formation; Azathioprine; Concanavalin A; Humans; Immunity, Cellular; Immunoglobulin G; In Vitro Techniques; Middle Aged; Multiple Sclerosis; Pokeweed Mitogens; T-Lymphocytes; T-Lymphocytes, Regulatory

Using in vitro lymphocyte proliferation induced by the phytomitogen concanavalin A (Con A), we investigated immune function and regulation in patients with myasthenia gravis (MG) and multiple sclerosis (MS). Unfractionated peripheral blood mononuclear cells of normal individuals responded to a wide range of ConA concentrations; the T cell fraction responded to a lesser degree and only to high concentrations. These findings suggest the presence of two receptors for ConA, one of high affinity present on a non-T cell accessory cell and the other of low affinity present on T cells. Contrasting defects in the level of response of unfractionated lymphocytes and T cells were found in patients with MG and MS. The peak response of T cells in the MG patients was 22.6 +/- 9.6 X 10(3) cpm (mean +/- SEM) compared with 54.6 +/- 6.5 X 10(3) for controls (p less than 0.05), while the response of unfractionated lymphocytes did not differ from that in controls. For MS patients, the unfractionated lymphocyte response was diminished: 56.3 +/-2.8 X 10(3) cpm versus 70.5 +/- 4.5 X 10(3) for controls (p less than 0.05), while the T cell response was normal. These results indicate a defect in the direct T cell response in MG; in contract, in MS the response requiring T cell-accessory cell interaction is abnormal.

Topics: Adult; Aged; Concanavalin A; Dose-Response Relationship, Drug; Humans; Lymphocyte Activation; Middle Aged; Monocytes; Multiple Sclerosis; Myasthenia Gravis; Rosette Formation; T-Lymphocytes

In vitro interferon (IFN) responses of peripheral blood leukocytes to measles virus and to other IFN inducers were determined for multiple sclerosis patients and normal donors. The group mean IFN response to measles virus was significantly lower in patients (15 units) than in normal donors (100 units), and a greater proportion of the patients failed to exhibit a significant IFN response. This defect was not specific for measles virus and was also observed consistently in response to Newcastle disease virus, Poly(I).Poly(C), and concanavalin A. The level of IFN response was not related to the clinical stage of disease.

Topics: Adult; Cells, Cultured; Concanavalin A; Humans; Interferon Inducers; Interferons; Leukocytes; Measles virus; Multiple Sclerosis; Newcastle disease virus; Poly C; Poly I

Patients with multiple sclerosis and matched controls were tested for lymphocyte stimulation response and induction of suppressor cell activity in response to concanavalin A (Con A) and antigens from axolemma or myelin. Of 17 stable patients, 6 failed to have a suppressor cell response activated by one of these brain cell antigens. Among the patients who lacked these suppressor responses, five had lymphocyte stimulation responses to the same antigens. All matched controls except for one had suppressor cell responses to these antigens and none responded with a positive cellular immune reaction. We found no difference in lymphoproliferative responses to Con A in patients and controls. The level of suppressor cell activity induced by Con A in the stable MS patients varied but did not differ significantly from that of controls.

Topics: Antigens; Autoantibodies; Autoimmune Diseases; Axons; Brain; Concanavalin A; Humans; Liver; Lymphocyte Activation; Microsomes; Multiple Sclerosis; Myelin Sheath; T-Lymphocytes, Regulatory

Lysosome proteins derived from peripheral blood granulocytes of patients with multiple sclerosis (MS), lupus erythematosus (LE), rheumatoid arthritis (RA) and recurrent uveitis cause the impairment of Con A-induced suppressor cell activity in two-step culture in vitro. This effect is independent of lysosome protease activity. Such a phenomenon, observed in vitro, may cause disturbances in suppressor cell function in the course of the above diseases.

Topics: Adult; Arthritis, Rheumatoid; Autoimmune Diseases; Concanavalin A; Female; Humans; Isoflurophate; Lupus Erythematosus, Systemic; Male; Middle Aged; Multiple Sclerosis; Neutrophils; Proteins; Recurrence; T-Lymphocytes, Regulatory; Uveitis

The lysosomal factors obtained from PMNL of healthy persons and patients with multiple sclerosis, systemic lupus erythematosus and other neurological diseases inhibited in vitro the generation of Con A-induced suppressor cell activity. The results obtained proved that these factors from granulocytes of MS-relapse and active LE have a stronger inhibitory effect on suppressor cell activity than on healthy ones.

Topics: Adult; Aged; Concanavalin A; Humans; Long-Term Care; Lupus Erythematosus, Systemic; Middle Aged; Multiple Sclerosis; Nervous System Diseases; Neutrophils; Proteins; T-Lymphocytes, Regulatory

Topics: Adult; Blood; Cells, Cultured; Central Nervous System Diseases; Concanavalin A; Female; Humans; Male; Middle Aged; Mitogens; Multiple Sclerosis; Phagocytes; Phytohemagglutinins; Pokeweed Mitogens; Thymidine

Topics: Concanavalin A; Dose-Response Relationship, Immunologic; Humans; Immunosuppression Therapy; Lymphocyte Activation; Lymphocytes; Multiple Sclerosis; Myelin Basic Protein; Phytohemagglutinins; T-Lymphocytes; Tuberculin

Peripheral blood lymphocytes from forty-nine patients with multiple sclerosis (MS), twelve patients with other neurological diseases and twenty-seven healthy individuals were examined by a two-stage procedure based on the Con A stimulation of the basic protein (BP) pre-treated lymphocytes. Enhanced BP-induced blastogenic stimulation (BS) (90--220% was observed in MS individual classified as active (A-MS), whereas suppressed BS (27--120%) was observed in MS patients classified as non-active (NA-MS). The difference was statistically significant (P less than 0.01). The results obtained with the MS patients' lymphocytes also differed significantly (P less than 0.05) from those of the two control groups. Either response obtained with MS lymphocytes could be elicited with a similar concentration of BP. The enhanced or suppressed response to BP did not correlate with the cellular response to common antigens such as candida and streptokinase-streptodornase. Most lymphocytes of individuals from the two control groups showed BS values of 100 +/- 20% in response to BP. However, some degree of stimulation or suppression was also obtained with lymphocytes from a few individuals of both control groups. The potential value and application of the two-stage procedure is discussed.

Topics: Adult; Aged; Concanavalin A; Female; Humans; Hypersensitivity, Delayed; Immunity, Cellular; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Multiple Sclerosis; Myelin Basic Protein

Lymphocytes from normal adult donors exposed in vitro to inactivated measles virus were found to exert significant suppression (33.9%) of the concanavalin A responses of cryopreserved, autochthonous responder cells. In marked contrast, lymphocytes from multiple sclerosis patients exhibited significantly reduced suppression (1.5%), and in 80% of cases failed to suppress at all. The degree of suppression increased slightly with age of the patient but did not vary with the clinical stage of disease. There was no apparent genetic restriction of suppressor activity. Although specificity of this phenomenon for measles virus has not been established, no differences in the responses of lymphocytes from normal or multiple sclerosis patient donors were found with subacute sclerosing panencephalitis, Sendai, canine distemper, mumps, or influenza viruses. Supernates of measles-treated lymphocytes from normal donors possessed both suppressive and antiviral activities. Both activities were resistant to pH 2 treatment and were neutralized by an anti-human leukocyte interferon antiserum, strongly suggesting that interferon (probably type I) was the mediator of suppression. Consistent with their inability to suppress concanavalin A responses, lymphocytes from multiple sclerosis patients failed to produce significant amounts of interferon in response to measles challenge in vitro. These results extend previous observations that multiple sclerosis patients are unable to respond appropriately to measles virus antigen in vitro.

Topics: Adult; Age Factors; Concanavalin A; Humans; Immunosuppression Therapy; Interferons; Measles virus; Multiple Sclerosis; T-Lymphocytes

Concanavalin A (Con A)-activated suppressor cell activity was determined in multiple sclerosis (MS) patients who had been assigned to one of three subgroups, those with active disease, those recovering from a flare-up, and those with stable disease. The level of suppression induced by the Con A-activated suppressor cells on the mitogenic response of autologous peripheral blood lymphocytes was reduced in patients with active disease (3 +/- 8%) compared with stable patients (30 +/- 8%), patients recovering from a flare-up (62 +/- 5%), and controls (40 +/- 5%). As a measure of the actual amounts of suppressor factors released, the effect of supernatants from the Con A-activated cells on the proliferative activity of a dividing cell line (L cells) was determined concurrently. The inhibitory effect of supernatants from activated cells was reduced in active and stable MS patients (7 +/- 3%) compared to controls (21 +/- 4%). Three of 4 with active MS showed mildly elevated immune complex levels as measured by the Raji cell technique; each of these patients had low suppressor activity. Levamisole (1 microgram per milliliter) failed to alter suppressor cell activity in our in vitro system.

Topics: Concanavalin A; Humans; Levamisole; Multiple Sclerosis; T-Lymphocytes

Suppression of the lymphocyte response to concanavalin A (Con A), phytohaemagglutinin (PHA) and protein A from Staphylococcus aureus (SpA) by Con A-induced suppressor cells was measured in twenty-four patients with recently active-recovering multiple sclerosis (MS), twelve with inactive MS and twenty-three healthy controls. Patients with recently active disease displayed significantly greater suppression of the response to Con A. Suppression of the responses to PHA and SpA did not differ among the groups. Lymphocyte stimulation in cultures not showing suppression was similar in all three types of subjects. These results suggest a disturbance of lymphocyte regulation in patients with recently active-recovering MS and illustrate the potential usefulness of measuring the suppression of responsiveness to several mitogens.

Topics: Adult; Concanavalin A; Female; Humans; Immunosuppression Therapy; Lymphocyte Activation; Male; Middle Aged; Mitogens; Multiple Sclerosis; Phytohemagglutinins; Staphylococcal Protein A; T-Lymphocytes

By means of a microculture technique and calculation of incorporation of 14C-thymidine, cerebrospinal fluid (CSF) lymphocytes from multiple sclerosis (MS) patients showed low or absent proliferation when stimulated with phytohaemagglutinin, concanavalin A, or pokeweed mitogen, in contrast to peripheral blood lymphocytes (PBL) obtained simultaneously and investigated in parallel. A lower proliferation of CSF lymphocytes compared with PBL was also found in acute aseptic meningitis, although it has been reported that CSF lymphocytes show greater proliferation than PBL when specifically stimulated. The low proliferation of MS CSF lymphocytes on mitogen stimulation may be a consequence of prolonged sensitization to an as yet unidentified antigen. The proliferation of MS CSF lymphocytes was not improved by adding irradiated PBL, making helper cell insufficiency less likely. MS CSF had no inhibitory effect on proliferation of PBL, arguing against an inhibitory effect of soluble factors in the CSF as an explanation for the depressed response of CSF lymphocytes.

Topics: Cells, Cultured; Concanavalin A; Female; Humans; Lymphocyte Activation; Lymphocytes; Male; Meningitis, Aseptic; Multiple Sclerosis; Phytohemagglutinins; Pokeweed Mitogens

A factor in the sera of multiple sclerosis patients inhibits RNA, protein and DNA synthesis in actively metabolizing mitogen stimulated lymphocytes. Inhibition of macromolecular synthesis precedes cell death by 24 to 36 hours. The factor is effective on cells which are already committed to transformation by previous exposure to mitogen and cells which are simultaneously exposed to the factor and mitogen. Previous exposure of unstimulated cells to the factor does not alter their subsequent response to mitogen. The factor does not inhibit RNA synthesis of unstimulated lymphocytes isolated on a Ficoll-Hypaque gradient, nor is it toxic to these cells.

Topics: Biological Products; Biological Transport; Cell Division; Cell Membrane; Concanavalin A; DNA; Humans; Lymphocyte Activation; Lymphocytes; Mitogens; Multiple Sclerosis; Phytohemagglutinins; Pokeweed Mitogens; Protein Biosynthesis; Receptors, Mitogen; RNA

Mitogen responsiveness and suppressor cell function were determined in patients with multiple sclerosis. Mitogen response to concanavalin A, expressed as stimulation index, decreased with age in both patients and controls. Although responses in the overall group of young patients did not differ from controls, the stimulation index was reduced in clinically inactive patients. Patients with recent flare-ups showed responses comparable to controls. Suppressor cell activity increased with age in both disease and control groups. Among young patients, suppressor activity was borderline low in inactive patients but increased significantly in those with recent exacerbations.

Topics: Adolescent; Adult; Age Factors; Aged; Concanavalin A; Herpes Simplex; Humans; Middle Aged; Mitogens; Multiple Sclerosis; T-Lymphocytes

Topics: Aged; Concanavalin A; Humans; Middle Aged; Multiple Sclerosis; Myasthenia Gravis; T-Lymphocytes