concanavalin-a and Acquired-Immunodeficiency-Syndrome

Parenteral nutrition is a part of the nutritional support regimen of patients with AIDS-associated wasting syndrome and gastrointestinal dysfunction. The cholesterol (CHOL) level in human immunodeficiency virus (HIV) membrane is very high, and recent lipid formulations with high phospholipid (PL) content have demonstrated the ability to trap CHOL from endogenous sources, modifying the composition of cell membranes. We administered lipid-based home parenteral nutrition for 3 mo to malnourished AIDS patients. The patients were randomly divided into two groups: 23 received the regular 20% fat emulsion formulation, and 27 received a 2% formulation enriched 10-fold with PLs but containing the same amount of triglycerides. All patients gained weight and improved their activity level. Those receiving the high-PL composition showed increased serum CHOL concentrations (from 147 to 241 mg/dL; P < 0.01), but no increase was seen in the number of CD4 cells or improvement in immune function. HIV infectivity was not modified. Patients receiving regular PLs had significantly decreased (P < 0.02) IgA concentrations (from 776 to 300 mg/dL) and improved mitogen response to phytohemagglutinin and to concanavalin A. This formula, too, had no effect on HIV infectivity. We conclude that standard parenteral nutritional influences the nutritional and immune status of malnourished AIDS patients. A PL-enriched parenteral formulation can trap CHOL, but it does not affect the immune profile or HIV infectivity in patients with advanced disease.

Topics: Acquired Immunodeficiency Syndrome; Adult; CD4 Lymphocyte Count; Cholesterol; Concanavalin A; Fat Emulsions, Intravenous; Humans; Immunoglobulin A; Middle Aged; Parenteral Nutrition, Home; Phospholipids; Phytohemagglutinins; Surveys and Questionnaires

We have shown a new phenomenon demonstrating that BALB/c female mice mated to C57BL/6 males during a year (7-10 pregnancies) develop AIDS-like disease or acute leukemia after an additional immunization with fixed ConA activated paternal (C57BL/6) lymphocytes. The AIDS-like disease is sexually and vertically transmissible and easily transferable to intact BALB/c and C57BL/6 mice by filtered plasma of affected animals.

Topics: Acquired Immunodeficiency Syndrome; Animals; Autoantibodies; Blood Component Transfusion; CD4-Positive T-Lymphocytes; Concanavalin A; Copulation; Crosses, Genetic; Female; Histocompatibility Antigens Class II; Immunization; Infectious Disease Transmission, Vertical; Interleukin-2; Leukemia, Experimental; Lymphocyte Activation; Lymphocyte Transfusion; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Pregnancy; Pregnancy Complications, Infectious; Retroviridae; Transplantation, Homologous

The antiretroviral efficacy and hematotoxicity of ribavirin, a guanosine analogue, have been evaluated in mice infected with the LP-BM5 virus pool [murine acquired immunodeficiency syndrome (MAIDS) model]. Doses ranging from 6.25 to 200 mg/kg/day were injected intraperitoneally twice a day for 6 weeks to infected mice. Drug treatment induced a significant protection against splenomegaly and lymphadenopathy at doses > or = 25 mg/kg. Moreover, doses starting at 50 mg/kg protected against hypergammaglobulinemia, minimized the loss of spleen CD8+ T cells, and reconstituted the capacity of splenocytes to proliferate in response to concanavalin A. The spleen and cervical lymph node architectures were protected, and a reduction in the emergence of germinal centers was observed at 50 mg/kg ribavirin. Hematotoxicity appeared at doses > or = 50 mg/kg ribavirin, and severe anemia was predominant only at doses of 100 and 200 mg/kg. This study shows that ribavirin protects mice against the effects resulting from retrovirus infection at doses of > or = 50 mg/kg in a MAIDS model and induces severe hematotoxicity at doses > or = 100 mg/kg.

Topics: Acquired Immunodeficiency Syndrome; Animals; Antiviral Agents; Blood Cell Count; CD4-CD8 Ratio; Cell Division; Concanavalin A; Disease Models, Animal; Female; Immunoglobulin M; Leukemia Virus, Murine; Lymph Nodes; Mice; Mice, Inbred C57BL; Murine Acquired Immunodeficiency Syndrome; Organ Size; Ribavirin; Spleen

Lymphocytes respond to mitogens, viruses and other activation agents with hydrogen peroxide or reactive oxygen bursts which may originate at or near the cell membrane. It has been shown that a very small increase in the ratio of Con A cells results in a rapid switchover from mitogenicity to cytotoxicity. It is hypothesized that the change from mitogenicity to cytotoxicity correlates with the strength and duration of the hydrogen peroxide or reactive oxygen bursts which in turn depends on the number of molecules of the activation agent bound per cell. This hypothesis is presented and discussed in the context of the apoptosis (programmed cell death) and pro-oxidant-antioxidant hypothesis of CD4+ T-cell and B-cell subpopulation depletion in AIDS.

Topics: Acquired Immunodeficiency Syndrome; Antioxidants; Apoptosis; B-Lymphocyte Subsets; CD4-Positive T-Lymphocytes; Concanavalin A; HIV Envelope Protein gp120; Humans; Hydrogen Peroxide; Leukemia, T-Cell; Lymphocytes; Measles virus; Mitosis; Models, Biological; Oxidants; Oxidative Stress; Reactive Oxygen Species; Signal Transduction; Tumor Cells, Cultured

We find that interleukin-2 (IL-2) production is severely depressed (80-90%) in AIDS T-cells (CD4+ or CD8+) stimulated with anti-CD3 or Con A together with phorbol ester (PMA) or anti-CD28 coactivation. Likewise, the proliferative response of CD4+ T-cells was suppressed, from a mean of 24.6% (HIV+) to 59.1% (AIDS) for PMA with activators OKT3 (anti-CD3), Con A, enterotoxin B or pokeweed mitogen, and 20.2% (HIV+) to 77.8% (AIDS) with anti-CD28 co-activation. Similar degrees of suppression were found with the CD8+ T-cells except for a much greater suppression at the HIV+ stage with anti-CD28 (57.7%), approximately 2.5 times higher than for PMA coactivation. However, when proliferation was induced by the two coactivators combined (PMA plus anti-CD28), much less suppression was observed: 8.5% (HIV+) to 19.0% (AIDS) for CD4+ cells and 8.2% to 26.5%, respectively, for CD8+ cells. The data suggest that during HIV infection the CD28 pathway becomes most defective, but can be bypassed to some extent by the less-impaired PMA pathway. The IL-2 (+PMA) signal in HIV+ and AIDS cells was also significantly less suppressed suggesting that the disregulation in HIV infection is more prominent prior to the IL-2 stage of the mitogenic pathway. It is remarkable that the CD4+ and CD8+ T-cells at both the HIV+ and AIDS stages generally show the same degree of suppression with all the various activators and coactivators used.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acquired Immunodeficiency Syndrome; Adult; CD28 Antigens; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Concanavalin A; Enterotoxins; Hispanic or Latino; HIV Infections; Humans; Interleukin-2; Lymphocyte Activation; Pokeweed Mitogens; Severity of Illness Index; T-Lymphocyte Subsets; Tetradecanoylphorbol Acetate

The neuropeptide substance P (SP) is known to increase cell-mediated immune responses in animal models and healthy subjects. Several studies have suggested an involvement of neuropeptides in the immunopathogenesis of some diseases. The study of the immunomodulatory effects of neuropeptides, namely SP, may represent a model for the analysis of immunoregulatory defects in HIV infection at the level of the interaction between the immune and nervous systems, both of which are known to be affected by the virus. In the present study, we investigate the possibility of a disturbance in the immunomodulatory properties of SP in HIV infection by analysing the effects of SP (10(-10)-10(-6) M) on the lymphocyte proliferative responses to concanavalin A (Con A) and phytohaemagglutinin (PHA) assessed by 3H-thymidine incorporation in peripheral blood lymphocytes from 34 HIV-infected patients (16 asymptomatic (ASY)/persistent generalized lymphadenopathy (PGL); 18 ARC/AIDS) and in 37 healthy subjects. In ASY/PGL HIV-infected patients, SP 10(-7) M was identified as the concentration inducing the maximal increase in the lymphocyte responses to Con A and PHA, similarly to what was observed in healthy subjects. In ARC/AIDS patients, SP appeared to inhibit the mitogenic responses, particularly those induced by Con A, in contrast to the effects found either in healthy subjects or in ASY/PGL patients. These results suggest the existence of an alteration in the in vitro immunomodulatory properties of SP in ARC/AIDS patients compared with healthy subjects and ASY/PGL patients. In conclusion, the unexpected finding of an inhibitory effect of SP on lymphocyte proliferation from ARC/AIDS patients justifies further investigation of the neuropeptide-dependent immunoregulatory systems in HIV infection.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; AIDS-Related Complex; CD4-Positive T-Lymphocytes; Concanavalin A; Female; HIV Infections; Humans; In Vitro Techniques; Lymphocyte Activation; Male; Middle Aged; Neuroimmunomodulation; Phytohemagglutinins; Substance P; T-Lymphocyte Subsets

To study the biological properties of the immunosuppressive peptide (ISU-peptide) of HIV-1, a 17-mer corresponding to the amino-acid domain 583-599 of the transmembrane glycoprotein gp41 of HIV-1. This peptide exhibits sequence homology to the highly conserved ISU-peptide of type C and D retroviruses. Also, to study the immune response against the corresponding gp41 epitope in AIDS patients.. The ISU-peptide and control peptides were synthesized and tested for immunosuppressive activity in different in vitro lymphocyte proliferation assays. Antibody responses were tested using a peptide enzyme-linked immunosorbent assay. A new property of the ISU-peptide, inhibition of HIV-1 replication, was investigated using a cytopathogenicity assay.. The ISU-peptide of HIV-1 and the immunosuppressive peptides of type C and type D retroviruses possess similar functional properties. They inhibit mitogen-induced and lymphokine-dependent T-lymphocyte proliferation, they are interspecies-reactive, they must be conjugated to a carrier protein in order to be immunosuppressive, and their N-terminal octamers represent the minimal immunosuppressive domain. HIV-infected individuals develop antibodies against an epitope located at the C-terminal end of the ISU-peptide and the number of responders and antibody titres decrease during progression to AIDS. In addition to its immunosuppressive activity, the ISU-peptide of HIV-1 inhibits the cytopathic effect of HIV-1 on human MT4 cells, suggesting interference with virus replication.. The immunosuppressive property of the ISU-peptide suggests that gp41 might contribute to the development of AIDS. The evolutionary conservation of the immunosuppressive domain and the ability of the corresponding ISU-peptide to inhibit HIV replication suggest that this domain plays an important role in the life cycle of HIV-1.

Topics: Acquired Immunodeficiency Syndrome; Amino Acid Sequence; Animals; Cell Line; Concanavalin A; Enzyme-Linked Immunosorbent Assay; HIV Envelope Protein gp41; HIV Seronegativity; HIV Seropositivity; HIV-1; Humans; Interleukin-2; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Peptide Fragments; Species Specificity; T-Lymphocytes

To elucidate relationship between disease progress and immunologic alteration in feline immunodeficiency virus (FIV) infection, we classified naturally infected cats into clinical stage groups using the working criteria modified from those for human immunodeficiency virus (HIV) infection. Among the five distinct stages described for HIV infection, the three phases; asymptomatic carrier (AC), AIDS related complex (ARC), and acquired immunodeficiency syndrome (AIDS), were evaluated for concanavalin A (Con A)-induced lymphocyte blastogenic activities by using glucose consumption assay. There was a significant decrease of lymphocyte response in AC phase. The loss of response became marked as the disease progressed to ARC and AIDS, with an almost complete loss of mitogen response in AIDS phase. In addition to the loss of a lymphocyte function, AIDS in FIV infection was characterized by marked emaciation, anemia or pancytopenia, and postmortem evidences of opportunistic infections and lymphoid depletion.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Animals; Carrier State; Cat Diseases; Cats; Concanavalin A; Female; Immunologic Deficiency Syndromes; Leukocyte Count; Lymphocyte Activation; Male; Retroviridae Infections

The murine model of acquired immunodeficiency disease was used to evaluate both the antiretroviral and antiherpetic activities of the acyclic nucleotide analog 9-(2-phosphonylmethoxyethyl)adenine (PMEA). The antiretroviral activity of PMEA was compared with that of azidothymidine (AZT) in mice receiving the drug either immediately after infection or at late times in disease progression. Both AZT (oral, 30 mg/kg) and PMEA (parenteral, 25 and 5 mg/kg) were effective in slowing the development of disease when administered daily beginning on the day of infection. In contrast, neither drug alone was effective in modifying disease outcome when administered several weeks after viral infection. Human recombinant alpha interferon (rhuIFN alpha-B/D at 5 x 10(7) U/kg) was also ineffective when administered late in the course of disease. However, when administered in combination, both alpha interferon and PMEA (25 mg/kg) were able to suppress disease progression even when treatment was initiated as late as 3 weeks postinfection. Mice that were immunocompromised due to LP-BM5 virus infection were highly susceptible to acute (lethal) infection with herpes simplex virus type 1, whereas their immunocompetent littermates were not. PMEA was as effective as acyclovir in the treatment of opportunistic herpes simplex virus type 1 infections in LP-BM5 virus-infected mice. Thus, like AZT, PMEA was effective against retrovirus infection, and, like acyclovir, PMEA was effective against herpes simplex virus type 1 infection. This gives PMEA the unique potential of being useful in the treatment of opportunistic herpes simplex virus infections as well as the underlying retroviral disease.

Topics: Acquired Immunodeficiency Syndrome; Adenine; Animals; Antiviral Agents; Concanavalin A; Herpes Simplex; Interferons; Mice; Mice, Inbred C57BL; Mitogens; Opportunistic Infections; Organophosphonates; Spleen; Zidovudine

The purified human immunodeficiency virus type-l (HIV-l) Tat protein inhibited lymphocyte proliferation induced by tetanus toxoid or Candida antigens by 66 to 97% at nanomolar concentrations of Tat. In contrast, Tat did not cause a significant reduction of lymphocyte proliferation in response to mitogens such as phytohemagglutinin or pokeweed mitogen. Inhibition was blocked by oxidation of the cysteine-rich region of Tat or by incubation with an antibody to Tat before the assay. A synthetic Tat peptide (residues 1 to 58) also inhibited antigen-stimulated proliferation. Experiments with H9 and U937 cell lines showed that Tat can easily enter both lymphocytes and monocytes. The specific inhibition of antigen-induced lymphocyte proliferation by Tat mimics the effect seen with lymphocytes from HIV-infected individuals and suggests that Tat might directly contribute to the immunosuppression associated with HIV infection.

Topics: Acquired Immunodeficiency Syndrome; Cells, Cultured; Concanavalin A; DNA Replication; Gene Products, tat; HeLa Cells; HIV-1; Humans; Immunosuppression Therapy; Lymphocyte Activation; Lymphocytes; Pokeweed Mitogens; Promoter Regions, Genetic; Recombinant Proteins; Staphylococcal Protein A; tat Gene Products, Human Immunodeficiency Virus; Trans-Activators; Transcriptional Activation

We have examined the ability of monocyte-derived macrophages from patients with AIDS and other HIV-related disorders to kill the intracellular pathogen Toxoplasma gondii. We have also examined the capacity of peripheral blood mononuclear cells from these patients to produce macrophage-activating and other lymphokines. The capacity to produce interleukin 2 and gamma interferon decreases from controls through asymptomatic seropositive subjects and lymphadenopathy groups A (benign) and B (prodromal) to AIDS. The decrease did not correlate precisely with the decrease in CD4+ cells in these patients. Monocyte-derived macrophages from asymptomatic HIV-infected subjects and lymphadenopathy patients showed a decreased ability to kill T. gondii after activation with recombinant gamma interferon; paradoxically, this was most striking for PGL group A. The defect was largely overcome by using Concanavalin A stimulated autologous supernatants. It was notable that macrophages from AIDS patients showed normal killing with recombinant gamma interferon, but that the supernatants from AIDS patients had reduced activity with normal macrophages. These studies confirm that functional defects of both lymphocytes and macrophages are found in HIV-infected subjects; they serve to emphasize the heterogeneity of the clinical and biological responses to this retrovirus, responses which have important implications in the pathogenesis and treatment of the immunodeficiency.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Concanavalin A; Humans; Interferon-gamma; Interleukin-2; Macrophage Activation; Macrophages; Male; Monocytes; T-Lymphocytes; Toxoplasma

Suppressor T-cell function was analyzed in seven children with acquired autoimmunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). Four of the patients had markedly increased serum IgG levels. All patients had elevated percentages and absolute numbers of peripheral blood T8 cells. In vitro concanavalin A generation of suppressor cells for T-cell mitogenic responses and suppression of pokeweed mitogen-driven immunoglobulin secretion were diminished in all patients. After intravenous treatment with gamma globulin, four patients regained in vitro suppression of pokeweed mitogen-driven gamma globulin secretion. Treatment with intravenous gamma globulin also modified in vitro suppressor T-cell functions in children with AIDS or ARC.

Topics: Acquired Immunodeficiency Syndrome; Child; Child, Preschool; Concanavalin A; Humans; Immunoglobulin G; Infant; Injections, Intravenous; Interleukin-2; L-Lactate Dehydrogenase; Suppressor Factors, Immunologic; T-Lymphocytes, Regulatory

The lymphocyte transformation responses to mitogens (phytohaemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM)), allogeneic cells, and the antigen-purified protein derivative (PPD) were studied in six acquired immunodeficiency syndrome (AIDS) patients and in six healthy controls, each of whom was HLA-DR- and mixed lymphocyte culture (MLC)-identical with one of the AIDS patients. No evidence of suppression was observed when irradiated or non-irradiated AIDS peripheral blood mononuclear cells (PBMC) were added to cultures of HLA-DR-identical PMBC from healthy controls stimulated with the strong mitogens PHA and Con A or with allogeneic cells, but suppression may be involved in the decreased responses in cultures stimulated with PWM or PPD. Addition of supernatants from macrocultures of AIDS cells did not suppress responses of control PBMC. Thus, suppression by any lymphocyte subset or soluble factor alone cannot explain the generally severely depressed transformation responses in AIDS. Addition of heavily irradiated HLA-DR-identical PBMC from healthy controls or supernatants from these cultures led to increased responses in cultures of mitogen-stimulated AIDS PBMC and in some cultures of antigen or allogeneic cell-stimulated AIDS PBMC, which were of the same magnitude as seen after the addition of commercially obtained T-cell growth factor (TCGF). This indicates that AIDS cells are deficient in producing TCGF. Heavily irradiated AIDS PBMC were capable of restoring the transformation responses to mitogens and antigens of purified HLA-DR-identical normal T cells, indicating that AIDS cells have a normal antigen-presenting capacity and interleukin (IL-1) production. However, AIDS PBMC had a very poor capacity to stimulate normal PBMC in MLC. Together, our experiments suggest that the immune deficiency in AIDS cells may be partially due to a decreased capability of T lymphocytes to produce TCGF and that a decreased number and/or function of dendritic cells may also be involved.

Topics: Acquired Immunodeficiency Syndrome; Adult; Concanavalin A; Histocompatibility Antigens Class II; Humans; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Male; Middle Aged; Phytohemagglutinins; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Tuberculin

The Celebes black macaque (Macaca nigra) colony at the Oregon Regional Primate Research Center has a high incidence of an immunodeficiency syndrome characterized by recurrent diarrhea and the development of retroperitoneal fibromatosis (RF). We have examined the relationship of type D viral infection to the immunodeficiency syndrome by surveying the colony for viral infection and for mitogen reactivity. Type D virus-positive monkeys (28% of the colony) have a higher prevalence of diarrhea, splenomegaly, lymphadenopathy and weight loss than do virus-negative monkeys, and RF has been found to occur only in virus-positive animals. Comparison of the concanavalin A (con-A) and phytohemagglutinin reactivities of the virus-positive and -negative populations has revealed no significant difference. However, within the virus-positive population, those with RF have reduced con-A reactivity and there are both high and low mitogen responders in the groups lacking RF. Thirty-two percent of the virus-positive monkeys are free of clinical symptoms, 40% have clinical symptoms but no RF, and 27% have clinical symptoms and RF. Five of the six monkeys with RF are older than the RF-free monkeys but monkeys are susceptible to type D retrovirus infection regardless of age or sex. The progressive nature of this immunodeficiency syndrome, its broad age range, and the probability that the etiological agent is also a type D retrovirus and the similarity of RF to Kaposi's sarcoma make this a potentially useful model for human AIDS.

Topics: Acquired Immunodeficiency Syndrome; Age Factors; Animals; Concanavalin A; Macaca; Mitogens; Monkey Diseases; Phytohemagglutinins; Retroviridae Infections

Persistent generalized lymphadenopathy (PGL) is observed predominantly in subjects at risk of developing AIDS. Twenty-seven individuals belonging to such groups: twelve homosexual males and fifteen intravenous drug users, were investigated for immunological abnormalities with particular attention to monocyte functions. They were compared with five AIDS patients. Twenty out of twenty-two individuals had anti-LAV/HTLV-III antibodies and most had abnormalities characteristic of AIDS: polyclonal hypergammaglobulinemia, decreased cell-mediated immunity, inverted T-cell helper/suppressor ratio and histological alterations of lymph nodes. As for peripheral blood monocyte functions, phagocytic capacity and production of O2- were normal and bactericidal capacity was decreased. Monocytes cultured in the presence of concanavalin A produced less PGE2 and more IL-1/MCF than normal monocytes. Similar abnormalities were found using monocytes from AIDS patients. These data suggest that monocytes from patients with PGL have functional alterations that may be either intrinsic or secondary to lymphocyte dysfunction(s); these alterations do not account for the decreased capacity of lymphocytes to respond to mitogens but may explain the uncontrolled activation of B cells.

Topics: Acquired Immunodeficiency Syndrome; Adult; Blood Bactericidal Activity; Cell Division; Concanavalin A; Dinoprostone; Female; Homosexuality; Humans; In Vitro Techniques; Interleukin-1; Lymphatic Diseases; Male; Middle Aged; Monocytes; Phagocytosis; Prostaglandins E; Substance-Related Disorders; Superoxides

Most retroviruses are immunosuppressive in vitro and in vivo. They are able to enhance virus-induced tumor development and/or to induce acquired immune deficiency syndromes (AIDS) which are characterized by malignant tumors and opportunistic infections. Experimental evidence for the immunosuppressive properties of several type D viruses derived from human cell lines and other retroviruses is presented.

Topics: Acquired Immunodeficiency Syndrome; Animals; Cattle; Concanavalin A; Haplorhini; Humans; Immune Tolerance; Lymphocyte Activation; Mice; Neoplasms; Neoplasms, Experimental; Phytohemagglutinins; Retroviridae; Species Specificity

Peripheral blood from patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) exhibits poor NK activity in the 51Cr-release assay. The present studies were undertaken to investigate the mechanism underlying the observed defective NK cytotoxic activity. On the basis of our studies on the mechanism of natural killer cell-mediated cytotoxicity (NKCMC), a defective NK cell can result from lack or decreased frequency of effector cells, inability to recognize and bind the target cell, failure to be activated for the release of NK cytotoxic factors (NKCF), and/or failure to synthesize or secrete NKCF. Each of these various possibilities was examined. Single cell analysis revealed that the frequency of NK cells was comparable to controls, and although the NK cells bind to the NK-sensitive target, the bound target is not lysed. These results suggested that the defect in NK cells was not due to depletion of NK cells or to a defect in recognition structures, but that it was located at the postrecognition event. We previously demonstrated that after binding to target, the NK cell is stimulated to release NKCF in the supernatants and NKCF lyse specifically NK-sensitive targets. Accordingly, we investigated the activation of NK cells from AIDS and ARC patients for release of NKCF. After coculture with the stimulator cell, the patients' NK cells failed to release active NKCF in the supernatant. However, the cells released NKCF after stimulation with the lectin Con A or a mixture of TPA and ionophore, albeit to a lesser extent than controls. These results suggested that AIDS and ARC NK cells are defective in the trigger involved in release of NKCF. Further studies were done to investigate whether the immunomodulator IL 2 can restore the functional activity of the defective NK cells. Treatment with IL 2 resulted in augmented NK cytolytic activity, but did not reach control levels of activated cells from normal controls. Furthermore, the patients' IL 2-treated cells recover partially the ability to be stimulated by NK cells and to release NKCF. These results suggest that the trigger for NKCF production and the cytolytic function of the patients' NK cells are regulated by IL 2. By delineating the stage at which the AIDS and ARC NK cells are defective, it is now possible to monitor their recovery and to investigate the effect of various biologic response modifiers in restoring NK activity.

Topics: Acquired Immunodeficiency Syndrome; Adjuvants, Immunologic; Concanavalin A; Cytotoxicity Tests, Immunologic; Cytotoxicity, Immunologic; Ethers; Humans; Interleukin-2; Ionomycin; Killer Cells, Natural; Killer Factors, Yeast; Male; Protein Biosynthesis; Proteins; Tetradecanoylphorbol Acetate

Regulation of natural killer (NK) activity of peripheral blood mononuclear cells (PBMC) from patients with the acquired immune deficiency syndrome (AIDS) and from individuals at high risk of developing AIDS (R-AIDS) was studied. The response of untreated PBMC to the interferon inducer polyinosinic polycytidilic acid (Poly I:C) was lower in AIDS and R-AIDS than in normal controls and PBMC from R-AIDS were more susceptible to stimulation with lymphokine rich supernatants (Con A-SN, PHA-SN, lectin free IL-2) than AIDS and normal controls. To determine the role of the different T lymphocyte subsets in the regulation of NK activity, PBMC were selectively treated with monoclonal non-cytotoxic anti-Leu 2a and anti-Leu 3a antibodies and then stimulated with lymphokine rich supernatants. These results indicate that the effect of crude supernatants was the combination of opposite effects. Leu 2a-blocked R-AIDS-PBMC enhanced NK cytotoxicity when exposed to IL-2 rich supernatants whereas Leu 3a-blocked R-AIDS-PBMC suppressed the cytotoxic reaction.

Topics: Acquired Immunodeficiency Syndrome; Concanavalin A; Cytotoxicity, Immunologic; Humans; In Vitro Techniques; Interleukin-2; Killer Cells, Natural; Lymphokines; Male; Poly I-C

Simian acquired immunodeficiency syndrome (SAIDS) was transmitted to four of four rhesus macaques with blood from rhesus macaques naturally infected with a type D retrovirus, simian retrovirus-2 (SRV-2). Three of the four blood recipients died with SAIDS at 13, 15, and 26 weeks postinoculation. The fourth animal is alive with SAIDS. All four test monkeys became viremic and produced antiviral antibody. None of the inoculated monkeys produced measureable neutralizing antibody to SRV-2. The survivor produced higher levels of antiviral antibody than the monkeys that died. Phytohemagglutinin and concanavalin A reactivity of peripheral blood lymphocytes was depressed from weeks 6 to 12 after inoculation. Clinical findings included development of splenomegaly in all four monkeys, and diarrhea in two monkeys. Blood counts remained within the normal range except for a depression in the number of polymorphonuclear lymphocytes in two monkeys. Hematocrits were decreased in two monkeys just prior to their death. All four test monkeys developed lymph node atrophy and bone marrow hypoplasia. Total proteins and immunoglobulin production were normal. This report provides evidence that SRV-2, as well as other type D retroviruses, causes SAIDS in macaque species.

Topics: Acquired Immunodeficiency Syndrome; Animals; Antibodies, Viral; Concanavalin A; Lymphocyte Activation; Lymphocytes; Lymphoproliferative Disorders; Macaca; Macaca mulatta; Monkey Diseases; Phytohemagglutinins; Retroviridae

To examine the defect in cellular immunity in patients with acquired immunodeficiency syndrome (AIDS), we studied in vitro lymphocyte proliferation and interferon (IFN) release in response to cytomegalovirus (CMV) antigen and Concanavalin A mitogen in 40 homosexual men with AIDS, 10 homosexual men with chronic lymphadenopathy syndrome, 7 healthy homosexual men, and 18 healthy heterosexual subjects of either sex. CMV serology by an enzyme-linked immunosorbent assay and viral cultures for CMV were performed. Lymphocytes of patients with AIDS showed impaired CMV-specific release of IFN but normal mitogen-induced IFN release. The defect was not attributable to CMV infection per se. Cell proliferation in response to both CMV antigen and mitogen was impaired in patients with AIDS who had opportunistic infections. The defect could not be attributed to CMV viremia. We concluded that impaired release of IFN in response to a viral antigen is characteristic of lymphocytes in patients with AIDS and that this defect is distinct from a defect in mitogenic responsiveness, which coexists predominantly in patients with opportunistic infections.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Antigens, Viral; Concanavalin A; Cytomegalovirus; Female; Humans; Interferons; Lymphocyte Activation; Male; Middle Aged

Immunological and mycological investigations were carried out in 21 Swedish homosexual males. One of them had AIDS, one pre-AIDS and 19 lymphadenopathy of whom 18 fulfilled the criteria of persistent generalized lymphadenopathy (PGL) as defined by the Centers for Disease Control, Atlanta, (CDC). The patients were investigated immunologically with respect to their in vitro lymphocyte reactivity to various mitogens. The patients with AIDS and pre-AIDS belonged to the group of 8 patients with low response to mitogens. Blood helper T cell percentages and serum beta 2-microglobulin concentrations correlated with the PHA reactivity. Three patients, with the diagnoses AIDS, pre-AIDS and PGL respectively, had clinical signs of oral candidiasis with rich growth of Candida albicans in culture. These were all low responders to mitogen stimulation. Six cases of tinea pedis were diagnosed and seemed to be distributed among the patients irrespectively of the severity of their immunological disorders.

Topics: Acquired Immunodeficiency Syndrome; Adult; beta 2-Microglobulin; Candidiasis, Oral; Concanavalin A; Dermatomycoses; Homosexuality; Humans; Lymphatic Diseases; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; Pokeweed Mitogens; T-Lymphocytes, Helper-Inducer; Tinea Pedis

In order to reveal the activity of polymorphonuclear neutrophil leukocytes (PMNL) representing the first step of defence against infections, measurements of chemiluminescence (CL) were performed in patients suffering from acquired immune deficiency syndrome (AIDS), lymphadenopathy, or hemophilia. In comparison with healthy controls, AIDS patients revealed significant reduction (about 50 per cent) of phagocytic, i.e. CL activity of neutrophils, which had been induced by Zymosan. Only part of the patients suffering from lymphadenopathy answered with decreased granulocyte activity on the application of Zymosan. If concanavalin A was used as stimulant of metabolic activity of PMNL-independently of phagocytosis-again AIDS and some of the lymphadenopathy patients showed a markedly reduced neutrophil response. In conclusion it should be stated that there is some evidence for at least two defects of cellular immunity associated with AIDS and to some extent, with AIDS-endangered homosexuals suffering from lymphadenopathy: first the defect of PMNL to answer to concanavalin A with increased metabolic activity, and secondly the defect of PMNL to start phagocytosis induced by Zymosan with a subsequent release of oxygen radicals which are measurable as chemiluminescence. The appraisal of granulocyte activity by means of measurements of chemiluminescence might become an additional criterion for AIDS diagnostics.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Anti-Infective Agents, Urinary; Concanavalin A; Drug Combinations; Hemophilia A; Humans; Immunoglobulins; Luminescent Measurements; Luminol; Lymphoproliferative Disorders; Male; Neutrophils; Phagocytosis; Sulfamethoxazole; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Zymosan

Herpesviral infections and cellular immunity were studied in 19 patients with acquired immunodeficiency syndrome who were treated with human lymphoblastoid interferon for Kaposi's sarcoma. Before treatment, cytomegalovirus (CMV) and Epstein-Barr virus were isolated from 18 of 19 patients and 13 of 14 patients, respectively. Serum levels of interferon were measurable in all cases. Concanavalin A induced lymphocyte proliferation normally in 16 of 18 patients, but CMV induced proliferation in only nine of 18 patients. Natural killer cell activity was normal in 12 of 19 patients and was augmented in vitro by interferon in six of 19 subjects. CMV-specific HLA-restricted cytotoxic T cell activity was found in only two of 15 cases. With therapy, serum levels of interferon increased in 15 of 18 patients. There were two partial tumor remissions but no improvements in viral infections. Natural killer cell activity was decreased in 11 of 14 cases, and in vitro augmentation by interferon was absent in all five previous responders. CMV-specific T cell activity did not improve, but HLA-unrestricted cytotoxicity was increased in four of eight cases.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antibodies, Viral; Antigens, Viral; Capsid Proteins; Concanavalin A; Cytomegalovirus; Cytomegalovirus Infections; Cytotoxicity, Immunologic; Herpesviridae Infections; Herpesvirus 4, Human; Homosexuality; Humans; Interferon Type I; Killer Cells, Natural; Lymphocyte Activation; Male; Middle Aged; Sarcoma, Kaposi

The production of the T cell lymphokine interleukin-2 (IL-2) was found to impaired in all of seven male patients with AIDS or homosexuals with persistent generalized lymphadenopathy (AIDS related complex, AIDS-RC) whom we studied. Conversely the T cell response to IL-2 was found unimpaired as was the production of the monocyte factor interleukin-1 (IL-1). The response of T cells to IL-1 was found markedly decreased in two of the four patients with AIDS and in two of the three patients with AIDS-RC. Five of six patients had flat curves in autologous mixed lymphocyte cultures with no significant proliferative response throughout 7 days. The exception was a Haitian heterosexual patient with AIDS. Natural killer cell function was decreased in three of four patients with AIDS and two of three patients with AIDS-RC but it augmented normally in the presence of IL-2 in four, including the two who had it normal basally. Responses to pokeweed mitogen were within normal limits in all seven patients despite decreased responses to concanavalin A and phytohaemagglutinin. These findings help pinpoint the defect in AIDS to the T4+ cell, and perhaps even to one of its subpopulations, and suggest a role for IL-2 in the treatment of AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Concanavalin A; Female; Humans; Interleukin-1; Interleukin-2; Killer Cells, Natural; Leukocyte Count; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Male; Mitosis; Phytohemagglutinins; Rosette Formation; T-Lymphocytes

Patients with the acquired immunodeficiency syndrome (AIDS) exhibit a variety of disorders of cellular immunity, including a deficient ability to generate cytotoxic T cells and depressed levels of natural killer (NK) cell activity. Interleukin 2 (IL 2) in vitro can markedly augment these depressed immune functions. Because IL 2 can induce the release of interferon-gamma (IFN-gamma) from normal peripheral blood lymphocytes (PBL), and because IFN-gamma may play a role in the regulation of NK cell activity, this study was performed to determine if the IL 2 enhancement of the NK cell activity of patients with AIDS was an IFN-gamma-dependent effect. PBL from eight healthy heterosexual donors and from nine patients with AIDS were studied for their ability to release IFN-gamma in response to IL 2 at a concentration of 100 U/ml. After 60 hr of culture, the PBL of all eight healthy donors produced IFN-gamma with a mean titer of 113 U/ml (range 40 to 320 U/ml). In contrast, the PBL from only two of nine patients with AIDS released measurable amounts of IFN-gamma (40 U/ml each) in response to IL 2 with a mean titer of 13.5 U/ml for all nine. Although the PBL from patients with AIDS were deficient in their capacity to produce IFN-gamma in response to 100 U/ml of IL 2, significant enhancement of NK cell activity could be obtained after only 1 hr of PBL treatment with 10 U/ml of IL 2, with an optimal NK enhancing effect occurring at doses of 50 to 100 U/ml of IL 2. The use of an anti-IFN-gamma monoclonal antibody resulted in complete neutralization of the IFN released from the normal PBL cultured with IL 2, but failed to inhibit the IL 2 enhancement of NK cell activity. Exogenous IFN-gamma exhibited different kinetics of enhancement of NK cell activity when compared to IL 2, requiring substantially more than 1 hr of pretreatment of PBL. These results indicate that the PBL from patients with AIDS usually do not release IFN-gamma when cultured with IL 2, and that IL 2 enhancement of the depressed NK cell activity of these patients may be an IFN-gamma-independent event. These results may have important implications for the therapy of AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adjuvants, Immunologic; Concanavalin A; Cytotoxicity, Immunologic; Humans; Interferon Inducers; Interferon-gamma; Interleukin-2; Killer Cells, Natural; Lymphocytes; Male

The type D retrovirus PMFV, derived from a human cell line, suppresses the in vitro response of human lymphocytes to different T-cell mitogens as well as the mixed lymphocyte reaction. The suppressive effect is virus-specific and the active fraction copurifies with the virus particles. The suppression is produced by both crude and highly purified intact and disrupted virus preparations. However, the suppressive activity of virus disrupted by ether or a detergent is higher as compared with intact virus. The absence of any factors cytotoxic for lymphocytes or lymphoblasts in the suppressive virus preparation is shown by different methods.

Topics: Acquired Immunodeficiency Syndrome; Cell Survival; Concanavalin A; Humans; Immune Tolerance; Immunosuppressive Agents; Lymphocyte Activation; Phytohemagglutinins; Retroviridae

The effect of indomethacin on mitogen-induced lymphocyte proliferative responses was studied in six normal heterosexual subjects and nine patients with the acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC). Indomethacin enhanced only Con A-induced lymphocyte responses in six heterosexual men. In contrast, study of the cells from AIDS and ARC revealed that indomethacin enhanced PHA-induced lymphocyte proliferative responses from 52,600 counts/min to 70,900 counts/min (P less than 0.005) and 81,400 counts/min (P less than 0.001) at 0.1 and 1 microgram/ml. respectively and increased Con A-induced lymphoproliferation from 30,800 counts/min to 52,000 counts/min (P less than 0.01) at 0.1 microgram/mg and 51,1000 counts/min (P less than 0.005) at 1 microgram/ml. These results suggest that indomethacin enhanced mitogen-induced lymphoproliferative responses in vitro with cells from patients with AIDS and AIDS-related complex and may have therapeutic potential in some patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adjuvants, Immunologic; Adult; Concanavalin A; Humans; In Vitro Techniques; Indomethacin; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; Pokeweed Mitogens

Topics: Acquired Immunodeficiency Syndrome; Concanavalin A; Diarrhea; Humans; Inosine; Inosine Pranobex; Lymphatic Diseases; Lymphocyte Activation; Phytohemagglutinins; Pokeweed Mitogens; T-Lymphocytes

Topics: Acquired Immunodeficiency Syndrome; Adult; Concanavalin A; Humans; Immunity, Cellular; Interleukin-2; Lymphocyte Activation; Male; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Supernatants from peripheral blood mononuclear cells obtained from certain patients with the acquired immune deficiency syndrome (AIDS) or its prodrome were capable of depressing spontaneous and pokeweed mitogen-driven B lymphocyte differentiation into plasmacytes, and the proliferative responses of T cells to specific antigen. These soluble suppressor factors (SSF) were present in uniquely high concentrations, with significant differences from healthy controls and from patients with various other conditions previously associated with factor-mediated immunosuppression. T cell-independent functions were not modified by SSF. Suppression was not genetically constrained, and did not appear to be mediated by cytotoxicity, prostaglandin, or alpha or gamma interferons. SSF was a product of the interaction of T lymphocytes with adherent cells. T cells or T cell factors from AIDS patients, but not from normal controls, could collaborate with control adherent cells in the formation of SSF. Restoration of DNA synthesis-independent differentiation of B lymphocytes into plasmacytes in SSF-treated cultures was realized by addition of reducing agents, such as 2-mercaptoethanol, on culture initiation. These data suggest inhibitory mechanisms possibly related to that of concanavalin A-induced soluble immune response suppression, and perhaps offer clues to clinically applicable substances which are potentially capable of mitigating such responses.

Topics: Acquired Immunodeficiency Syndrome; Adult; Cell Adhesion; Cell Division; Cells, Cultured; Concanavalin A; Female; Humans; Immunoglobulin G; Immunoglobulin M; Lymphocyte Activation; Lymphokines; Male; Middle Aged; Monocytes; Suppressor Factors, Immunologic; T-Lymphocytes