myelin-basic-protein and Encephalomyelitis

Topics: Animals; Antibodies, Monoclonal; Arthritis, Experimental; Autoantibodies; Autoimmune Diseases; DNA; Encephalomyelitis; Humans; Hybridomas; Immunity, Cellular; Immunoglobulin Idiotypes; Insulin Antibodies; Major Histocompatibility Complex; Mice; Myelin Basic Protein; Rats; Receptors, Antigen, T-Cell; T-Lymphocytes

Topics: Animals; Antibody Formation; Antigens; Autoimmune Diseases; Cell Migration Inhibition; Cyclophosphamide; Disease Models, Animal; Encephalomyelitis; Guinea Pigs; Haplorhini; Humans; Immunity, Cellular; Immunization; Immunoglobulin G; Lymphocyte Activation; Methotrexate; Multiple Sclerosis; Myelin Basic Protein; Nerve Tissue Proteins; Protein Binding; Rabbits; Rats; Skin Tests; Virus Diseases

Japanese macaque encephalomyelitis (JME) is an inflammatory demyelinating disease that occurs spontaneously in a colony of Japanese macaques (JM) at the Oregon National Primate Research Center. Animals with JME display clinical signs resembling multiple sclerosis (MS), and magnetic resonance imaging reveals multiple T2-weighted hyperintensities and gadolinium-enhancing lesions in the central nervous system (CNS). Here we undertook studies to determine if JME possesses features of an immune-mediated disease in the CNS. Comparable to MS, the CNS of animals with JME contain active lesions positive for IL-17, CD4+ T cells with Th1 and Th17 phenotypes, CD8+ T cells, and positive CSF findings.

Topics: Animals; Antigens, CD; B-Lymphocytes; Central Nervous System; Cytokines; Disease Models, Animal; Encephalomyelitis; Lymphocytes; Macaca; Macrophages; Magnetic Resonance Imaging; Microfilament Proteins; Microglia; Multiple Sclerosis; Myelin Basic Protein; Nerve Tissue Proteins

An immuno-enzyme assay of NSE and MBP in the cerebrospinal fluid (CFS) and blood serum of rats during the development of acute experimental autoimmune encephalomyelitis revealed the increase of NSE, a neuronal marker, and MBP, a marker for myelin. The investigation has shown that the increased level of NSE in CSF was prior to the increased concentration of MBP. The changes of these neurospecific proteins (NSP) in the serum were not the same as in the CSF. The analysis of the ratio between NSP concentrations in CSF to serum revealed the initial marked decrease of BBB permeability to MBP but not to NSE.

Topics: Acute Disease; Animals; Autoimmune Diseases; Biomarkers; Blood-Brain Barrier; Disease Models, Animal; Encephalomyelitis; Female; Myelin Basic Protein; Nerve Tissue Proteins; Oligodendroglia; Phosphopyruvate Hydratase; Rats; Rats, Sprague-Dawley; Severity of Illness Index; Transcription Factors

Limited remyelination is a key feature of demyelinating Theiler's murine encephalomyelitis (TME). It is hypothesized that a dysregulation of differentiation of oligodendroglial progenitor cells (OPCs) represents the main cause of insufficient regeneration in this model of multiple sclerosis.. TME virus (TMEV)-infected SJL/J mice were evaluated by footprint analysis, light and electron microscopy, immunohistology, confocal immunofluorescence and RT-qPCR at multiple time points ranging from 1 h to 196 days post infection (dpi).. Footprint analysis revealed a significantly decreased stride length at 147 and 196 dpi. Demyelination progressively increased from 14 towards 196 dpi. A mild amount of remyelination was detected at 147 and 196 dpi. Early onset axonal injury was detected from 14 dpi on. TMEV RNA was detectable throughout the observation period and markedly increased between 7 and 28 dpi. Intralesional nerve/glial antigen 2 (NG2)-positive OPCs were temporarily increased between 28 and 98 dpi. Similarly, a transient upregulation of NG2 and platelet-derived growth factor alpha-receptor mRNA was noticed. In contrast, intralesional 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)-positive oligodendrocytes were decreased between 56 and 196 dpi. Although CNPase mRNA remained unchanged, myelin basic protein mRNA and especially its exon 2 containing splice variants were decreased. Glial fibrillary acidic protein (GFAP)-positive astrocytes and GFAP mRNA were increased in the late phase of TME. A mildly increased colocalization of both NG2/CNPase and NG2/GFAP was revealed at 196 dpi.. Summarized, the present results indicated a dysregulation of OPC maturation as the main cause for the delayed and limited remyelination in TME. A shift of OPC differentiation from oligodendroglial towards astrocytic differentiation is postulated.

Topics: 2',3'-Cyclic-Nucleotide Phosphodiesterases; Animals; Antigens; Cardiovirus Infections; Cell Differentiation; Encephalomyelitis; Female; Gene Expression; Glial Fibrillary Acidic Protein; Immunohistochemistry; Mice; Microscopy, Confocal; Microscopy, Electron; Microscopy, Fluorescence; Multiple Sclerosis; Myelin Basic Protein; Myelin Sheath; Nerve Tissue Proteins; Oligodendroglia; Proteoglycans; Receptor, Platelet-Derived Growth Factor alpha; RNA, Messenger; Spinal Cord; Stem Cells; Theilovirus

Lewis rats immunized with myelin basic protein (MBP) develop experimental autoimmune encephalomyelitis (EAE) and associated anterior uveitis (AU), which recurs. The goal was to analyze cellular activation markers and adhesion molecules of T cells that infiltrate the eyes and spinal cord during acute and recurrent AU in actively and passively induced diseases simultaneously in the same animals.. EAE-AU was induced in Lewis rats by immunization with MBP in CFA, or by adoptive transfer of MBP-specific T-cell lines, and the signs of clinical EAE and AU was scored. Cells isolated from the iris-ciliary body were tested by flow cytometry for expression of CD4, CD8, CD45RC, T-cell receptor (TCR) Vbeta8.2, alpha4 integrin, L-selectin, CD44, and CD134.. Ocular T cells showed a significantly higher expression of CD62L (l-selectin) than did T cells in the spinal cord. In addition, a much lower percentage of infiltrating CD8(+) T cells was found in the eyes during AU. In passive transfer experiments, T-cell lines derived from acute and recurrent uveitis showing similar phenotypes differing in specificities but possessed the capacity of inducing both AU and EAE. Pretreatment of rats with effector CD4(+) T cell before MBP immunization did not induce suppression of EAE or AU. However, pretreatment with regulatory CD8(+) T cells significantly reduced the severity and duration of both EAE and AU.. T cells recruited into the inflamed eyes or central nervous system (CNS) are mainly activated/memory T cells expressing different levels of L-selectin. Regulatory CD8(+) T cells may contribute to the susceptibility of the eye to recurrent AU. The differences in phenotypes of T cells recruited simultaneously to two different organs suggest that microenvironment also plays a role in determining lymphocyte homing.

Topics: Adoptive Transfer; Animals; Antigens, CD; Autoimmune Diseases; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Movement; Ciliary Body; Encephalomyelitis; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Immunophenotyping; Integrin alpha4; Iris; L-Selectin; Lymphocyte Activation; Myelin Basic Protein; Rats; Rats, Inbred Lew; Receptors, Antigen, T-Cell, alpha-beta; Recurrence; Uveitis, Anterior

To determine the contribution of B cells to brain myelin injury in Semliki Forest Virus (SFV) encephalomyelitis, normal C57BL/6 (B6) and B-cell-deficient (C57BL/6-tm1Cgn) B6 mice were infected with SFV. The peak of clinical disease, i.e., the time at which the greatest proportions of mice had moderate to severe clinical signs, appeared earlier in B6 mice [day 7 postinfection (pi)] than in B-cell-deficient mice (day 21 pi). By flow cytometry, no clear differences were found in the percentages of CD3(+)CD4(+) T cells in the brains of B6 and B-cell-deficient mice. However, by day 21 pi, percentages of CD3(+)CD8(+) T cells were greater in brains of B-cell-deficient than in those of B6 mice. On day 21 pi, percentages of CD19(+) B cells were maximal in B6 mice, but B cells were absent in B-cell-deficient mice at all time points. Sera obtained from B6 mice showed antibody responses to SFV, to SFV E2 peptides p137-151 and p115-133, and to peptides of myelin oligodendrocyte glycoprotein p18-32 and myelin basic protein (MBP) p64-75. Sera obtained from B-cell-deficient mice showed minimal or no reactivity to SFV, E2, or myelin peptides. CNS inflammatory and PAS-positive macrophage foci were maximal on days 7-14 pi in all mice. Additionally, B6 mice had brain white matter vacuolation, whereas B-cell-deficient mice did not. These data suggest that brain infiltrating B cells and anti-myelin antibodies contribute to myelin injury in SFV encephalomyelitis.

Topics: Alphavirus Infections; Amino Acid Sequence; Animals; Antibodies, Viral; B-Lymphocytes; Brain; Encephalomyelitis; Lymphocyte Subsets; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Molecular Sequence Data; Myelin Basic Protein; Myelin Proteins; Myelin Sheath; Myelin-Associated Glycoprotein; Myelin-Oligodendrocyte Glycoprotein; Peptide Fragments; Semliki forest virus; T-Lymphocytes; Viral Proteins

SJL mice are susceptible to inflammatory autoimmune diseases of the central nervous system (CNS), while BALB/c mice are relatively resistant. To understand differences in immune responses that may contribute to autoimmune neurologic disease, we compared the responses of SJL and BALB/c mice to infection with Sindbis virus, a virus that causes acute nonfatal encephalomyelitis in both strains of mice. Clearance of virus was similar, but SJL mice developed a more intense inflammatory response in the brain and spinal cord and inflammation persisted for several weeks. Analysis of lymphocytes isolated from brains early after infection showed an absence of NK cells in SJL mice, while both strains of mice showed CD4+ and CD8+ T cells. During the second week after infection, CD4+ T cells increased in SJL mice and the proportion of CD8+ T cells decreased, while the opposite pattern was seen in BALB/c mice. Expression of IL-10 mRNA was higher and IL-4 mRNA was lower in the brains of infected SJL than in BALB/c mice, while expression of the mRNAs of IL-6, IL-1beta, TNFalpha, and the Th1 cytokines IL-2, IL-12, and IFN-gamma was similar. Lymphocytes isolated from the CNS of SJL mice produced large amounts of IL-10. CNS lymphocytes from both strains of mice produced IFN-gamma in response to stimulation with Sindbis virus, but not in response to myelin basic protein. These data suggest that IL-10-producing CD4+ T cells are differentially recruited to or regulated within the CNS of SJL mice compared with BALB/c mice infected with Sindbis virus, a characteristic that may be related to low levels of IL-4, and is likely to be involved in susceptibility of SJL mice to CNS inflammatory diseases.

Topics: Alphavirus Infections; Animals; Apoptosis; Base Sequence; CD4-Positive T-Lymphocytes; DNA Primers; Encephalomyelitis; Female; Interleukin-10; Interleukin-4; Killer Cells, Natural; Mice; Mice, Inbred BALB C; Myelin Basic Protein; RNA, Messenger; Sindbis Virus; Species Specificity; Time Factors; Virus Replication

Regulatory sequences used in plasmids for naked DNA vaccination can modulate cytokine production in vivo. We demonstrate here that injection of plasmid DNA can suppress the prototypic T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis, by inducing IFN-gamma.

Topics: Animals; Autoimmune Diseases; Encephalomyelitis; Female; Interferon-gamma; Lymph Nodes; Multiple Sclerosis; Myelin Basic Protein; Plasmids; Rats; Rats, Inbred Lew; Spleen; Vaccines, DNA

Inflammation of multiple sclerosis (MS) brain and spinal cord tissue consists of macrophages, T lymphocytes and cytokines as well as B lymphocytes and immunoglobulins (IgGs). IgG can be detected in high concentrations in both central nervous system tissue and cerebrospinal fluid (CSF). Using a sensitive radioimmunoassay (RIA), autoantibodies to myelin basic protein (anti-MBP) can be detected in the CSF of 90-95% of MS patients with active disease. The purpose of the present report was to determine whether these same autoantibodies can be reliably detected in non-MS patients. Between 1978 and 1998, CSF was collected from 1,968 control non-MS patients with psychiatric, inflammatory and noninflammatory neurological diseases as well as nonneurological systemic diseases, and anti-MBP were measured by the same RIA used to detect anti-MBP in MS CSF. Anti-MBP were undetectable in 98% of CSF samples from non-MS controls. In the remaining 2% of control samples, CSF IgGs capable of binding to MBP in vitro were unpredictably detected. This latter group included 1% of patients with miscellaneous diseases such as encephalomyelitis, 5 siblings with familial spastic paraparesis, rare patients with strokes, Wernicke-Korsakoff's syndrome, inherited leukodystrophy, motor neuron disease and some patients with miscellaneous spinal cord diseases. An additional 1% of patients included a group with neurological symptoms suggestive of early or predisseminated MS. The high prevalence of free and/or bound anti-MBP in the CSF of MS patients and the rare and unpredictable occurrence in the CSF of non-MS patients suggest that autoimmunity to MBP may be operative in the demyelination of MS. Molecular clones of anti-MBP with specificity towards variable surface or cryptic MBP epitopes in vivo may determine whether or not they are involved in the demyelinating process, and this variability may also be present within the MS population. Potential mechanisms of anti-MBP-mediated demyelination in MS patients are discussed.

Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Central Nervous System Diseases; Cerebrovascular Disorders; Child; Encephalomyelitis; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Myelin Basic Protein; Neurodegenerative Diseases; Sclerosis; Spinal Cord Diseases

We explore here if vaccination with DNA encoding an autoantigenic peptide can suppress autoimmune disease. For this purpose we used experimental autoimmune encephalomyelitis (EAE), which is an autoaggressive disease in the central nervous system and an animal model for multiple sclerosis. Lewis rats were vaccinated with DNA encoding an encephalitogenic T cell epitope, guinea pig myelin basic protein peptide 68-85 (MBP68-85), before induction of EAE with MBP68-85 in complete Freund's adjuvant. Compared to vaccination with a control DNA construct, the vaccination suppressed clinical and histopathological signs of EAE, and reduced the interferon gamma production after challenge with MBP68-85. Targeting of the gene product to Fc of IgG was essential for this effect. There were no signs of a Th2 cytokine bias. Our data suggest that DNA vaccines encoding autoantigenic peptides may be useful tools in controlling autoimmune disease.

Topics: Animals; Autoimmune Diseases; DNA; Encephalomyelitis; Guinea Pigs; Immunoglobulin Fc Fragments; Myelin Basic Protein; Peptide Fragments; Plasmids; Rats; Rats, Inbred Lew; T-Lymphocytes; Vaccines, DNA

Myelin basic protein (MBP)-specific T cells are implicated in the pathogenesis of multiple sclerosis and are targets of selective immunotherapies. However, autoantigen-specific T cells can also be isolated from healthy individuals. Their functional potential is unknown and obviously cannot be tested in humans. We approached this question in a closely related primate species, the rhesus monkey. CD4+ T cell lines specific for MBP were isolated from normal rhesus monkeys using the same primary limiting dilution technique that is now widely used to generate human autoreactive T cell clones in vitro. Three different epitopes were recognized by three rhesus T cell lines isolated from three different monkeys. Upon activation, all lines produced interferon-gamma, interleukin-2, tumor necrosis factor-alpha, and granulocyte/macrophage colony-stimulating factor but neither interleukin-4 nor transforming growth factor-beta. The MBP-specific T cells were injected intravenously without adjuvant into the nonirradiated autologous monkey. One of the three rhesus monkeys developed an encephalomyelitis with a pleocytosis in the spinal fluid and perivascular infiltrates in the leptomeninges, spinal nerve roots and cerebral cortex. The data demonstrate that the normal immune repertoire of a primate species contains MBP-specific CD4+ T cells that are able to induce an autoimmune encephalomyelitis upon transfer into the nonirradiated autologous recipient.

Topics: Animals; Autoimmune Diseases; Cell Line; Cell Separation; Cytokines; Encephalomyelitis; Epitopes; Female; Macaca mulatta; Male; Myelin Basic Protein; Reference Values; T-Lymphocytes

Theiler's virus persists in the white matter of the spinal cord of genetically susceptible mice and causes primary demyelination. The virus persists in macrophages/microglial cells, but also in oligodendrocytes, the myelin-forming cells. Susceptibility/resistance to this chronic infection has been mapped to several loci including one tentatively located in the telomeric region of chromosome 18, close to the myelin basic protein locus (Mbp locus). To determine if the MBP gene influences viral persistence, we inoculated C3H mice bearing the shiverer mutation, a 20-kb deletion in the gene. Whereas control C3H mice were of intermediate susceptibility, C3H mice heterozygous for the mutation were very susceptible, and those homozygous for the mutation were completely resistant. This resistance was not immune mediated. Furthermore, C3H/101H mice homozygous for a point mutation in the gene coding for the proteolipid protein of myelin, the rumpshaker mutation, were resistant. These results strongly support the view that oligodendrocytes are a necessary viral target for the establishment of a persistent infection by Theiler's virus.

Topics: Animals; B-Lymphocytes; Cardiovirus Infections; Central Nervous System; Encephalomyelitis; Female; Genetic Predisposition to Disease; Lymphocyte Count; Male; Mice; Mice, Inbred C3H; Mice, Mutant Strains; Myelin Basic Protein; Oligodendroglia; RNA, Viral; Sequence Deletion; T-Lymphocytes; Theilovirus; Virus Latency

Following induction of experimental encephalomyelitis with a T-cell clone, L10C1, that is specific for the myelin basic protein epitope p87-99, the inflammatory infiltrate in the central nervous system contains a diverse collection of T cells with heterogeneous receptors. We show here that when clone L10C1 is tolerized in vivo with an analogue of p87-99, established paralysis is reversed, inflammatory infiltrates regress, and the heterogeneous T-cell infiltrate disappears from the brain, with only the T-cell clones that incited disease remaining in the original lesions. We found that antibody raised against interleukin-4 reversed the tolerance induced by the altered peptide ligand. Treatment with this altered peptide ligand selectively silences pathogenic T cells and actively signals for the efflux of other T cells recruited to the site of disease as a result of the production of interleukin-4 and the reduction of tumour-necrosis factor-alpha in the lesion.

Topics: Amino Acid Sequence; Animals; Base Sequence; Brain; Encephalomyelitis; Epitopes; Immune Tolerance; Interleukin-4; Mice; Molecular Sequence Data; Myelin Basic Protein; Paralysis; Peptide Fragments; T-Lymphocytes

Although the clonal selection theory states that lymphocytes should bear only a single specificity of receptor, there is much evidence that some T cells, at least, bear two receptors. Here, we have used mice transgenic for genes encoding an autoreactive T-cell receptor (TCR) to examine the specificity of T cells bearing two functional TCRs. We find that T cells developing in mice that do not express the major histocompatibility complex (MHC) molecule recognized as self by the transgene-encoded TCR express both this TCR and a second TCR that is specific for the MHC molecules of the strain in which it arose. Thus, these T cells have two TCRs, each specific for a distinct antigen bound to a distinct MHC molecule. In contrast, when raised in mice bearing the MHC for which the receptor is specific, T cells develop that express the transgene-encoded TCR almost exclusively. Such mice are highly susceptible to autoimmune disease. Our data suggest that on most T cells bearing two TCRs, only one is specific for peptides bound to self-MHC molecules and, thus, that expression of two TCRs does not usually confer reactivity to two unrelated antigens.

Topics: Animals; Autoimmune Diseases; Autoimmunity; Clone Cells; Encephalomyelitis; Flow Cytometry; H-2 Antigens; Lymphocyte Activation; Major Histocompatibility Complex; Mice; Mice, Inbred C57BL; Mice, Transgenic; Myelin Basic Protein; Peptide Fragments; Receptors, Antigen, T-Cell; Selection, Genetic; Spleen; T-Lymphocytes; Thymus Gland

A 9-year-old girl had hemiparesis, and a diagnosis of primary Sjögren syndrome was made. The neurologic dysfunction was multifocal, involving both the brain and spinal cord, and was recurrent; the findings mimicked multiple sclerosis. Corticosteroid treatment during episodes of acute neurologic dysfunction appeared to be beneficial.

Topics: Brain; Child; Diagnosis, Differential; Encephalomyelitis; Female; Hemiplegia; Humans; Immunoglobulin G; Magnetic Resonance Imaging; Multiple Sclerosis; Myelin Basic Protein; Prednisolone; Sjogren's Syndrome; Spinal Cord Diseases; Tomography, X-Ray Computed

We have generated TCR transgenic mice (T/R+) specific for myelin basic protein (MBP) and crossed them to RAG-1-deficient mice to obtain mice (T/R-) that have T cells expressing the transgenic TCR but no other lymphocytes. Both T/R+ and T/R- mice carry, in the lymph nodes and spleen, large numbers of the potentially encephalitogenic CD4+ anti-MBP T cells. These cells respond to MBP in vitro but show no signs of activation in vivo. Nevertheless, approximately 14% of H-2u T/R+ and 100% of H-2u T/R- mice developed spontaneous experimental autoimmune encephalomyelitis (EAE) within 12 months. These data indicate that EAE can be mediated by CD4+ anti-MBP T cells in the absence of any other lymphocytes and that nontransgenic lymphocytes that are present in T/R+ but absent in T/R- mice have a protective effect. The data also suggest that spontaneous EAE may be triggered by an in situ activation of CD4+ anti-MBP cells in the nervous system.

Topics: Amino Acid Sequence; Animals; Autoimmune Diseases; Central Nervous System; Crosses, Genetic; Encephalomyelitis; Flow Cytometry; Homeodomain Proteins; Immunohistochemistry; Lymphocyte Activation; Lymphocytes; Mice; Mice, Transgenic; Molecular Sequence Data; Myelin Basic Protein; Proteins; Receptors, Antigen, T-Cell, alpha-beta; Spleen

Autoreactive T cells specific for myelin basic protein (MBP), a major component of central nervous system (CNS) protein, are frequently found in blood and cerebrospinal fluid of patients with postinfectious encephalomyelitis. This autoimmune syndrome is a CNS complication after infections with a number of different enveloped viruses, e.g. mumps, measles, rubella, influenza and varicella. However, the pathophysiological mechanism leading to this breaking of natural self tolerance in the course of viral infection remains an enigma. A long-lasting hypothesis has suggested that incorporation of cellular (self) proteins into the envelope of budding viruses might be a possible mechanism leading to autosensitization. In a model study we demonstrate here that vesicular stomatitis virus (VSV), grown in myelin protein-expressing cell cultures, is highly efficient in triggering T cell responses to MBP in vitro and can prime autoreactive T cell immune responses in vivo. On the basis of these findings, we suggest that incorporation of CNS membrane components into the viral envelope and subsequent priming of self-reactive immune responses might be the common pathogenic mechanism underlying the postinfectious encephalomyelitis syndrome.

Topics: Amino Acid Sequence; Animals; Autoimmune Diseases; Autoimmunity; CD4-Positive T-Lymphocytes; Cell Line; Cells, Cultured; Disease Models, Animal; Encephalomyelitis; Humans; Mice; Molecular Sequence Data; Myelin Basic Protein; Rats; Rats, Inbred Lew; Vesicular stomatitis Indiana virus; Virus Replication

Our previous study using bromodeoxyuridine (BrdU) has shown that T cells in lesions of experimental autoimmune encephalomyelitis (EAE) in the rat central nervous system (CNS) lose their proliferating capability immediately after infiltration into the CNS. To characterize the nature of this phenomenon in more detail, we have isolated T cells from EAE lesions and examined their surface phenotype and response to encephalitogenic antigen, myelin basic protein (MBP). By flow cytometry (FCM) analysis, it was revealed that compared with peripheral blood lymphocytes, up-regulation of interleukin-2 (IL-2) receptors (0.06%-->3.73%) and the lymphocyte function-associated antigen-1 (LFA-1) molecules (0.76%-->17.6%) on spinal cord T cells (SCT) was observed. In spite of the latter finding suggesting that SCT are activated, SCT recovered from rats with full-blown EAE responded very poorly to MBP. The addition of thymocytes or thymocytes plus astrocytes did not alter the low responsiveness of SCT. More importantly, astrocytes strongly suppressed the response of lymph node T cells to MBP. Using MBP-specific T-line cells, it was revealed that T-cell suppression might be induced by incomplete presentation of MBP and release of suppressive humoral factors by astrocytes. Since the response of SCT was still poor when assayed after three and 12 rounds of stimulation with the antigen and propagation with IL-2, this phenomenon is long lasting. These findings are consistent with the findings obtained by the BrdU study that infiltrating T cells into the CNS do not proliferate vigorously. Taken together, the poor response of infiltrating T cells to MBP would be induced by co-existing cells such as astrocytes although the T cells are in an active form as judged by their surface phenotype. The present study suggests that activation of non-haematopoietic parenchymal cells in each organ by infiltrating T cells and subsequent inactivation of the T cells are important healing processes for organ-specific autoimmune diseases.

Topics: Animals; Antigens, Surface; Astrocytes; Autoimmune Diseases; Cell Division; Encephalomyelitis; Immune Tolerance; Immunoenzyme Techniques; Lymph Nodes; Myelin Basic Protein; Rats; Rats, Inbred Lew; Spinal Cord; T-Lymphocytes

The minimum structural requirements for peptide interactions with major histocompatibility complex (MHC) class II molecules and with T cell receptors (TCRs) were examined. In this report we show that substituting alanines at all but five amino acids in the myelin basic protein (MBP) peptide Ac1-11 does not alter its ability to bind A alpha uA beta u (MHC class II molecules), to stimulate specific T cells and, surprisingly, to induce experimental autoimmune encephalomyelitis (EAE) in (PL/J x SJL/J)F1 mice. Most other amino acid side chains in the Ac1-11 peptide are essentially irrelevant for T cell stimulation and for disease induction. Further analysis revealed that binding to A alpha uA beta u occurred with a peptide that consists mainly of alanines and only three of the original residues of Ac1-11. Moreover, when used as a coimmunogen with MBP Ac1-11, this peptide inhibited EAE. The finding that a specific in vivo response can be generated by a peptide containing only five native residues provides evidence that disease-inducing TCRs recognize only a very short sequence of the MHC-bound peptide.

Topics: Amino Acid Sequence; Animals; Autoimmune Diseases; Encephalomyelitis; Histocompatibility Antigens Class II; Mice; Molecular Sequence Data; Myelin Basic Protein; Peptides; Receptors, Antigen, T-Cell

Development of neurologic complications after Semple rabies vaccine is closely linked to development of antibody to myelin basic protein (MBP). The portions of MBP against which the antibodies are directed were analyzed by enzyme immunoassay in sera and cerebrospinal fluid from 27 patients with vaccine complications. Most of the antibody was directed to regions of MBP peptides 45-89 and 90-170. There was no apparent correlation between antibody specificity for MBP peptides 1-44, 45-89 and 90-170 and the type of post-vaccinal neurologic complication. We conclude that the immunoglobulin repertoire in human B lymphocytes for responding to human MBP favors the portion of the MBP molecule containing residues 45-170.

Topics: Antibodies; Encephalomyelitis; Humans; Immunoenzyme Techniques; Myelin Basic Protein; Nervous System Diseases; Neuropeptides; Rabies Vaccines

This is the first description of acute demyelinating experimental autoimmune encephalomyelitis (EAE) induced in rats by myelin basic protein (BP)-specific T lymphocytes without the administration of demyelinating antibodies. BP-specific T cell lines were selected from inbred Buffalo-strain rats (Rt-1b) following techniques used to develop similar lines from Lewis rats (Rt-1l). Unlike those of Lewis rats, the spinal cords of Buffalo rats with T cell line-mediated EAE had prominent perivascular demyelination associated with mononuclear inflammation. Like Lewis rat lines. Buffalo rat BP-specific T cell lines transferred acute, non-relapsing EAE into syngeneic recipients, demonstrating that demyelination in passive acute EAE can occur without subsequent clinical relapses.

Topics: Animals; Autoimmune Diseases; Cell Line; Demyelinating Diseases; Encephalomyelitis; Female; Guinea Pigs; Hypersensitivity, Delayed; Immunotherapy, Adoptive; Myelin Basic Protein; Rats; Rats, Inbred BUF; Rats, Inbred Lew; Spinal Cord; T-Lymphocytes

Beagle dogs were experimentally infected with the Cornell A75-17 strain of canine distemper virus. At three time points post-infection (PI), immunoreactive myelin basic protein (MBP) was measured in cerebrospinal fluid (CSF). Levels were correlated with neuropathological findings, interferon in CSF and virus isolation from the brain. CSF from animals inoculated with Cornell A75-17 strain often showed detectable immunoreactive MBP late in the disease course. As anticipated from earlier morphological studies, CSF drawn around day 20 PI lacked MBP while subsequent samples were positive. Dogs with severe demyelination had elevated values of immunoreactive MBP while dogs with only mild inflammation had little or none. Release of MBP or MBP peptides into CSF of dogs with canine distemper may be a valuable laboratory test in studies of the natural history of this disease and in assessing the response to treatment. Whether an immune response to MBP plays an immunopathogenic role in the chronic, demyelinating phase of canine distemper encephalitis remains to be determined.

Topics: Animals; Brain; Demyelinating Diseases; Distemper; Distemper Virus, Canine; Dogs; Encephalomyelitis; Myelin Basic Protein

The premise that acute non-fatal viral infections of the central nervous system (CNS) predispose to the subsequent development of chronic immune-mediated neurologic disease was investigated. Adult C57Bl/6 mice inoculated peripherally with 10(4) PFU of the A774 strain of Semliki Forest virus (SFV) develop a transient encephalomyelitis and sporadic (less than 20%) mild symptoms of paralysis with demyelination in the cerebellum from which they recover. Such recovered mice were found to develop signs characteristic of experimental allergic encephalomyelitis (EAE) 2 to 8 wk after either immunization with myelin basic protein (MBP) or receipt of 1 to 2 X 10(7) lymph node cells from MBP-primed syngeneic donors. These two methods of disease induction were unsuccessful when applied to normal B6 mice or those previously inoculated with noninfectious SFV. These findings suggest the possibility that virus-induced damage to CNS tissue may facilitate subsequent priming or clonal expansion of pre-existing myelin-reactive lymphoid cells.

Topics: Acute Disease; Animals; Demyelinating Diseases; Disease Susceptibility; Encephalomyelitis; Encephalomyelitis, Autoimmune, Experimental; Female; Immunization, Passive; Mice; Mice, Inbred C57BL; Myelin Basic Protein; Semliki forest virus; Togaviridae Infections

T cells were directly cloned from autopsied MS brain plaque tissue and reactivity was measured with the major encephalitogenic neuroantigens, myelin basic protein (MBP), and proteolipid protein (PLP). Control clones were simultaneously derived from the blood. The proportion of T4+ and T8+ T cell clones from the brain tissue differed from that of peripheral blood T cell clones derived at the same time, suggesting that the clones were not derived from the peripheral blood. None of 57 brain-derived T cell clones proliferated to either MBP or PLP, although they responded well to PHA and IL 2. An additional 235 clones derived from the cerebrospinal fluid and 126 clones from the peripheral blood of other subjects with multiple sclerosis also did not proliferate to MBP or PLP. In contrast, five of nine T4+ clones from the CSF of a subject with postinfectious encephalomyelitis exhibited low but clear reactivity to human MBP, supporting the possible role of MBP as the target antigen in this disease. These studies, the first to clone T cells directly from MS plaque tissue, suggest that the lack of consistent T cell reactivity to MBP or PLP in the peripheral blood of MS patients does not appear to be secondary to the sequestration of a large number of these cells in the brain.

Topics: Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; Brain; Cells, Cultured; Cerebrospinal Fluid; Clone Cells; Encephalomyelitis; Humans; Interleukin-2; Lymphocyte Activation; Multiple Sclerosis; Myelin Basic Protein; Myelin Proteins; Myelin Proteolipid Protein; Phytohemagglutinins; Proteolipids; T-Lymphocytes

Lewis and Brown Norway rats were infected at different ages with the neurotropic murine coronavirus strain, JHM and the resultant central nervous system diseases were studied. Suckling rats of both strains came down with a fatal, acute encephalomyelitis. Weanling Lewis rats developed a subacute demyelinating encephalomyelitis which neuropathologically revealed changes of an immunopathologic reaction. In contrast, Brown Norway rats developed a clinically silent subacute demyelinating encephalomyelitis with a persistent JHM virus infection which was less severe and quite different from the subacute demyelinating encephalomyelitis in Lewis rats with respect to size, distribution, and localization of the demyelinating plaques as well as the type of infiltrating cells. In addition, infected Lewis rats showed a pronounced lymphocyte proliferation to myelin basic protein and JHM virus whereas lymphocytes from infected Brown Norway rats did not react to these two antigens. These observations demonstrate the pathogenetic importance of host factors in the development of virus-induced demyelination.

Topics: Aging; Animals; Animals, Newborn; Antigens, Viral; Brain; Coronaviridae; Coronaviridae Infections; Demyelinating Diseases; Encephalomyelitis; Immunity, Cellular; Mice; Microscopy, Electron; Myelin Basic Protein; Rats; Rats, Inbred BN; Rats, Inbred Lew; Species Specificity; Spinal Cord

Post-infectious or post-vaccinal demyelinating encephalomyelitis and neuritis may be due to immunological cross-reactions evoked by specific viral antigenic determinants (epitopes) that are homologous to regions in the target myelins of the central and peripheral nervous systems. Such homologies have been found by computer searches in which decapeptides in two human myelin proteins were compared with proteins of viruses known to infect humans. These viruses include measles, Epstein-Barr, influenza A and B, and others that cause upper respiratory infections. Several regions identified in myelin basic protein and P2 protein can be related to experimental allergic encephalomyelitis or neuritis in laboratory animals.

Topics: Animals; Base Sequence; Chickens; Encephalomyelitis; Epitopes; Guinea Pigs; Haplorhini; Humans; Measles; Myelin Basic Protein; Myelin P2 Protein; Neuritis; Rabbits; Rats; Rats, Inbred Lew; Viral Proteins; Viral Vaccines

An electroimmunoblotting technique was used with a monoclonal antibody to myelin basic protein (MBP) to assess demyelination in 3 defined regions of the spinal cord in rats with acute experimental autoimmune encephalomyelitis (EAE). A slight loss in MBP was detected only in the sacrococcygeal region of the spinal cord after the onset of clinical signs. In all 3 spinal cord regions studied, significantly elevated levels of albumin and IgG were detected during the course of EAE by the same technique. At the onset of clinical signs, the levels of IgG and albumin were highest in the more caudal regions of the spinal cord. As the clinical signs became more severe, IgG and albumin levels increased in the more cranial regions of the spinal cord. These changes thus correlated with the ascending progression of clinical signs typical of EAE in rats. These results provided added evidence that in rats affected with acute EAE, the clinical signs occur independently of demyelination and coincide with vasogenic edema.

Topics: Albumins; Animals; Blood Physiological Phenomena; Encephalomyelitis; Female; Immunoglobulin G; Immunologic Techniques; Male; Myelin Basic Protein; Permeability; Rats; Rats, Inbred Strains; Spinal Cord

The loss of myelin-associated glycoprotein (MAG) and myelin basic protein (MBP) was compared by quantitative immunocytochemistry in demyelinating lesions of measles encephalomyelitis (ME), multiple sclerosis (MS), and progressive multifocal leukoencephalopathy (PML). Serial sections from paraffin-embedded tissue were reacted with antisera for MAG and MBP, and areas of staining loss were compared morphometrically. Lesions in ME showed MAG loss equal to that of MBP, lesions of PML showed MAG loss greater than that of MBP, and MS lesions showed a mixture of patterns. These data demonstrate distinctive patterns of MAG and MBP loss in these three diseases.

Topics: Central Nervous System; Demyelinating Diseases; Encephalomyelitis; Humans; Immunoenzyme Techniques; Leukoencephalopathy, Progressive Multifocal; Measles; Multiple Sclerosis; Myelin Basic Protein; Myelin Proteins; Myelin Sheath; Myelin-Associated Glycoprotein; Nerve Fibers, Myelinated

In the present report we provide the strain distribution patterns of susceptibility to acute mouse hepatitis virus type-4 (MHV-4) encephalomyelitis, acute experimental allergic encephalomyelitis (EAE) and vasoactive amine sensitivity (VAAS) for 9 (CXJ) recombinant-inbred strains between BALB/cKe (C) and SJL/J(J) mice. We confirm that susceptibility to MHV-4 is not linked to the H-2 complex, and that all strains susceptible to acute EAE have both a responder H-2 haplotype (H-2s or H-2d) and induced (B. pertussis) VAAS. In addition, we provide evidence that susceptibility to acute EAE induction is controlled by an additional presently unmapped locus and that an EAE-like histopathological disease does not usually follow MHV-4 infection intracerebrally in animals susceptible to MHV-4, acute EAE and induced VAAS.

Topics: Animals; Bordetella pertussis; Drug Hypersensitivity; Encephalomyelitis; Encephalomyelitis, Autoimmune, Experimental; Female; H-2 Antigens; Haploidy; Hepatitis, Viral, Animal; Histamine; Humans; Immunity, Innate; Male; Mice; Mice, Inbred Strains; Murine hepatitis virus; Myelin Basic Protein; Rats

We studied 19 patients with postinfectious encephalomyelitis complicating natural measles-virus infections, and our results support the hypothesis that this demyelinating disease has a pathogenesis similar to that of experimental allergic encephalomyelitis. Early myelin destruction was demonstrated by the presence of myelin basic protein in cerebrospinal fluid, and lymphocyte proliferative responses to myelin basic protein were found in 8 of 17 patients tested. A lack of intrathecal synthesis of antibody against measles virus suggests that measles encephalomyelitis may not be dependent on virus replication within the central nervous system. Similar lymphoproliferative responses to myelin basic protein of lymphocytes from single patients with encephalomyelitis after rabies vaccine or after varicella or rubella virus infections suggest a common immune-mediated pathogenesis for the perivenular demyelinating disease that can follow the injection of neural tissues or infection by a variety of viruses.

Topics: Adolescent; Adult; Child; Child, Preschool; Encephalomyelitis; Female; Humans; Immunoglobulins; Infant; Lymphocyte Activation; Male; Measles; Myelin Basic Protein; Virus Replication

Measles encephalomyelitis appears to be an immune-mediated parainfectious disorder, but it is unclear whether viral invasion of brain is an obligate step in its development. Immunocytochemical methods were used to search for virus antigen in formalin-fixed, paraffin-embedded central nervous system (CNS) tissues from 10 patients with measles encephalomyelitis and 12 patients who had died of measles without CNS involvement. All the CNS tissues studied were viral antigen negative. Similarly fixed CNS tissues from all of 6 patients with subacute sclerosing panencephalitis were viral antigen positive and served as controls. The pattern of perivenular demyelination was also determined in 4 cases of measles encephalomyelitis using antibodies to myelin associated glycoprotein and myelin basic protein and a Luxol fast blue stain. Areas of demyelination in serial sections were quantitated, and no morphometrical differences were found among tissues stained with the three stains. The data suggest the lack of virus replication in the CNS during encephalomyelitis or fatal measles without CNS symptoms. The pattern of loss of myelin associated glycoprotein and myelin basic protein in regions of perivenular demyelination resembles that reported in experimental allergic encephalomyelitis. This pattern of demyelination has been proposed to result from a primary attack on the myelin sheath rather than from direct involvement of the oligodendroglial cell.

Topics: Adolescent; Adult; Antigens, Viral; Brain; Child; Child, Preschool; Encephalomyelitis; Female; Humans; Male; Measles; Measles virus; Myelin Basic Protein; Myelin Proteins; Myelin Sheath; Myelin-Associated Glycoprotein

Topics: Adult; Animals; Autoantigens; Brain; Cell- and Tissue-Based Therapy; Encephalitis; Encephalomyelitis; Gangliosides; Humans; Immunoglobulin G; Lymphocyte Activation; Male; Myelin Basic Protein; Nerve Tissue; Polyradiculoneuropathy; Swine

The mechanism of suppression of experimental allergic encephalomyelitis (EAE) induced in Lewis rats by pretreatment with myelin basic protein (MBP) coupled to syngeneic spleen leukocytes (SL) was examined. Studies on the kinetics of the tolerance induction showed that pretreatment with MBP-SL suppressed EAE if given 7 but not 3 days before the disease-inducing injection of MBP in Freund's complete adjuvant. Treatment with cyclophosphamide 48 hr before administration of MBP-SL completely abolished the suppression of EAE. Transfer of lymph node and spleen cells from MBP-syngeneic erythrocyte conjugate (MBP-RBC) but not MBP-SL-pretreated rats resulted in suppression of disease in recipients subsequently given a disease-inducing injection of MBP. Administration of MBP coupled to SL from the histocompatible rat strain F344 resulted in suppression of the MBP-induced proliferative response of spleen cells from Lewis rats which had been given a disease-inducing injection of MBP. Taken together these results are consistent with the suppression of EAE induced by MBP-SL being mediated by suppressor T cells.

Topics: Animals; Encephalomyelitis; Female; Immunosuppression Therapy; Lymph Nodes; Lymphocyte Activation; Lymphocytes; Myelin Basic Protein; Rats; Rats, Inbred F344; Rats, Inbred Lew; Spleen

Cellular transfer of experimental autoimmune encephalomyelitis (EAE) was effected in mice with lymph node cells (LNC) from appropriately immunized donors. Pretreatment of LNC with anti-Lyt-1 and Lyt-2,3 antibodies indicated that the transfer of both EAE and a cell-mediated immune response in vitro to MBP was dependent on a subpopulation of T lymphocytes expressing the phenotype associated with the helper and cell-mediated delayed hypersensitivity functions, Lyt-1+, 2-.

Topics: Animals; Autoimmune Diseases; Encephalomyelitis; Female; Immunity, Cellular; Immunization, Passive; Male; Mice; Mice, Inbred BALB C; Mice, Inbred Strains; Myelin Basic Protein; T-Lymphocytes

In MS, there are many mechanisms by which viruses can produce demyelinating diseases in humans and experimental demyelinating infections in animals.

Topics: Brain; Distemper Virus, Canine; Encephalomyelitis; Humans; Leukoencephalopathy, Progressive Multifocal; Maus Elberfeld virus; Multiple Sclerosis; Murine hepatitis virus; Myelin Basic Protein; Myelin Sheath; Oligodendroglia; Spinal Cord; Virus Replication; Viruses; Visna-maedi virus

Experimental allergic encephalomyelitis (EAE) and other analogous neuroimmunologic diseases of animals and humans, including multiple sclerosis (MS), are discussed within the context of 1) host lymphoid cells autoreactive with myelin basic protein (MBP) or other neural antigens that elude normal immunoregulatory mechanisms, 2) development of subsets of cytotoxic effector cell clones directed against MBP and other central nervous system (CNS) antigenic components, and 3) neurophysiological and CNS inflammatory structural changes, respectively, which reflect the binding of these effector cell subsets to host CNS target tissue. One set of cytotoxic cells reactive with MBP appears to cause increased permeability of the cerebrovasculature with deposition of fibrin, development of edema, and appearance of clinical paralytic signs of EAE, unaccompanied by infiltrating host inflammatory cells. A second subset of cytotoxic effector cells reactive with non-MBP neural antigen(s) appears to cause the focal, perivascular host inflammatory cell response, which in turn leads to various degrees of demyelination, an important feature of EAE, and the identifying hallmark of the MS process. Indirect evidence, secured by a sensitive radioimmunoassay (RIA), implicates endogenous circulating MBP serum factors (MBP-SFs), characterized by high-affinity binding to anti-MBP antibodies represented in the RIA reagent antiserum, as being of paramount importance in preventing proliferation of neuroreactive cytotoxic lymphoid cells. In this sense MBP-SFs act as neuroautotolerogens. Based on the foregoing concepts and observations, major pathways of CNS injury and inflammation are postulated and discussed.

Topics: Animals; Brain; Encephalomyelitis; Encephalomyelitis, Autoimmune, Experimental; Fibrin; Humans; Lymphocytes; Multiple Sclerosis; Myelin Basic Protein; Myelin Proteins; Rats; Rats, Inbred Lew

Genetic control has been studied of the response to the encephalitogenic nonapeptide (NP) determinant of myelin basic protein (BP) in inbred guinea pigs of strains resistant or susceptible to induction of experimental autoimmune encephalomyelitis (EAE). By studying bone marrow-reconstituted animals, we found that susceptibility to induction of EAE was a function of the genotype of the cells of the lymphohematopoietic system and not of the physiological environment or target organ. Analysis of the T cell response showed that susceptible strains 13 or (2 X 13)F1 hybrid guinea pigs recognized the NP determinant when injected with whole BP in adjuvant. Resistant strain 2 guinea pigs responded to undefined determinants on BP, but not to the NP moiety. We investigated the cells involved in regulating the response to the NP determinant by injecting susceptible F1 hybrids with BP-pulse macrophages of either parental strain. Susceptible strain 13 macrophages triggered a response to the NP determinant and induced clinical EAE. In contrast, F1 animals injected with resistant strain 2 macrophages failed to respond to the NP determinant, although the macrophages were capable of presenting other undefined determinants present on whole BP. Therefore, genetic control of the immune response to the NP determinant appears to be exerted at the level of antigen presentation by macrophages to T lymphocytes.

Topics: Animals; Autoimmune Diseases; Bone Marrow Transplantation; Cell Communication; Crosses, Genetic; Encephalomyelitis; Epitopes; Genotype; Guinea Pigs; Hybridization, Genetic; Lymphocytes; Macrophages; Myelin Basic Protein; Peptides; Tuberculin

Topics: Animals; Antigens; Autoimmune Diseases; Carrier Proteins; Chickens; Chorionic Gonadotropin; Encephalomyelitis; Female; Humans; Immunoglobulin Idiotypes; Lymphocytes; Mice; Mice, Inbred Strains; Myelin Basic Protein; Papio; Rabbits; T-Lymphocytes; Thyroglobulin; Thyroid Gland; Thyroiditis; Thyroiditis, Autoimmune

Cellular immune responses to brain antigens in patients with head injury were studied by applying the leukocyte adherence inhibition (LAI) assay. The investigation was conducted in three phases. 1) In the initial phase, evaluation of a series of 22 test and 25 control cases obtained at random during a 2- to 6-week time frame following a traumatic event indicated significant non-adherence of leukocytes (NAL) in 77% of the test group and 20% of the control group in the presence of brain antigen. 2) In a second phase, larger test population was divided into four groups of different posttraumatic intervals. This study measured NAL in the presence of normal heart of normal brain antigen. Assays revealed an initial significant NAL in the presence of both antigens; however, after the first week following injury the majority of cases manifested significant NAL only with brain antigen. These values of NAL persisted over a 6- to 8-week period. 3) As a final phase of investigation, analysis of a sequential series of assays in 12 patients over a 90-day period indicated significant NAL in the presence of brain antigen within the first week of injury, this was followed by a drop in NAL in most of the cases. Studies at 7 to 60 days posttrauma demonstrated significant NAL with brain antigen alone, with a subsequent drop by 90 days. These observations are interpreted to represent sensitization of leukocyte subgroups to brain proteins that are immunologically recognized following the traumatic event.

Topics: Antibody Formation; Antigens; Autoantigens; Brain; Brain Injuries; Encephalomyelitis; Humans; Immunity, Cellular; Leukocyte Adherence Inhibition Test; Myelin Basic Protein; Time Factors

After intracranial replication of a neurotropic strain of vaccinia in mouse brain, analysis of the purified virus preparation reveals the presence of at least one host protein on the virus which was identified as the myelin basic protein. Vaccinia virus Elstree, a dermotropic virus may substitute for complete Freund's adjuvant (CFA) in inducing experimental allergic encephalomyelitis (EAE). Guinea pigs challenged with virus-myelin emulsions without CFA developed clinical and histological signs of EAE.

Topics: Adjuvants, Immunologic; Animals; Brain; Disease Models, Animal; Encephalomyelitis; Encephalomyelitis, Autoimmune, Experimental; Guinea Pigs; Mice; Myelin Basic Protein; Vaccinia; Vaccinia virus

Topics: Encephalomyelitis; Epitopes; Models, Biological; Myelin Basic Protein

Lymphocytes from patients with acute transverse myelopathy (ATM) were shown to undergo a specific and significant transformation when cultured in vitro in the presence of either the central nervous myelin basic encephalitogenic protein (BE) or the peripheral nerve myelin P2 protein. A similar pattern of response was demonstrated in acute disseminated encephalomyelitis and in acute myeloradiculitis. Lymphocytes from patients suffering from other autoimmune neurological disorders or other neurological diseases affecting the spinal cord showed no response to there immunologically related antigens, which have previously been found to have the capacity of inducing experimental allergic encephalomyelitis, either alone or with experimental allergic neuritis, when injected into animals. The specific in vitro response to BE and P2 suggests that in vivo sensitization of lymphocytes to such self-antigens occurs in ATM and than a cell-mediated, probably postinfecious autoimmune mechanism may be an important factor in the pathogenesis of the disease.

Topics: Acute Disease; Adolescent; Adult; Autoimmune Diseases; Encephalomyelitis; Female; Humans; Immunity, Cellular; Lymphocyte Activation; Male; Middle Aged; Myelin Basic Protein; Myelin Proteins; Myelitis; Myelitis, Transverse

Topics: Acute Disease; Antibodies; Brain Diseases; Chronic Disease; Encephalomyelitis; Female; Humans; Immunity, Cellular; Immunodiffusion; Iodine Radioisotopes; Lectins; Lymphocyte Activation; Male; Multiple Sclerosis; Myelin Basic Protein; Polyradiculopathy; Tritium

Topics: Amino Acids; Animals; Brain Chemistry; Chloroform; Citrates; Electrophoresis, Disc; Encephalomyelitis; Evaluation Studies as Topic; Guinea Pigs; Humans; Immune Sera; Methanol; Methods; Myelin Basic Protein; Myelin Sheath; Nerve Tissue Proteins; Trypsin