Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An immunospot assay that detects single secretory cells was used to enumerate interferon-gamma secreting cells (IFN-gamma-sc) in mononuclear cell suspensions from the central nervous system (CNS) and peripheral lymphoid organs after actively induced experimental allergic encephalomyelitis (EAE) in Lewis rats. In the CNS compartment there was a significant increase in the number of IFN-gamma-sc preceding the onset of the clinical signs of EAE. Both in rats with EAE and rats immunized with Freund's complete adjuvant (FCA) the number of IFN-gamma-sc increased in peripheral lymphoid organs, as compared to non-immunized controls. In view of the potent immunoregulatory effects of IFN-gamma, its intra-CNS secretion may play a crucial role for clinicopathological events in EAE. To study the numbers of primed T cells that in response to myelin antigens produced IFN-gamma, mononuclear cell suspensions from peripheral lymphoid organs were precultured to allow for antigen uptake, presentation and T cell triggering, followed by enumeration of IFN-gamma-sc. T cells responding to a peptide of myelin basic protein (MBP) that previously have been shown encephalitogenic in Lewis rats, appeared initially and were quantitatively dominant over the course of EAE. Later, T cell reactivities to multiple regions of MBP appeared, showing that the concept of immunodominance in EAE is non-absolute and time dependent. Splenocyte cultures from EAE rats exposed to the different antigens showed a reduced number of IFN-gamma-sc compared to cultures not exposed to antigen, suggesting an antigen-induced suppression of T cell effector molecules.
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PMID:T cell immunity and interferon-gamma secretion during experimental allergic encephalomyelitis in Lewis rats. 170 16

Splenic T cells from myelin basic protein (MBP)-immunised Lewis rats were activated to transfer experimental autoimmune encephalomyelitis (EAE) by co-culture with MBP-pulsed lymphoid dendritic cells (DC). MBP-pulsed DC could be kept for at least 24 h at 37 degrees C in antigen-free medium without affecting their ability subsequently to activate encephalitogenic T cells. However, MBP-pulsed DC were rendered much less stimulatory after a 6 h, but not 2 h, secondary incubation with ovalbumin. Thus, although encephalitogenic complexes between MBP and DC appear very stable in the absence of competing antigens, in their presence, antigen exchange can take place over a period of a few hours; this has positive implications for therapy of EAE by antigen competition.
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PMID:Competitive dissociation of encephalitogenic complexes between antigen presenting cells and myelin basic protein. 171 39

We have recently reported that experimental autoimmune encephalomyelitis (EAE) can be suppressed by the oral administration of myelin basic protein (MBP). The oral introduction of 20 mg MBP together with a trypsin inhibitor results in inhibition of EAE clinical signs, decreased CNS histopathologic changes and dramatically reduced MBP-specific proliferative responses in fed and challenged Lewis rats. In the present study, we have investigated the mechanism underlying MBP-induced oral tolerance in EAE. Neither lymphoid cells (lymph node cells, spleen cells, Peyer's patch lymphocytes, thymocytes) nor humoral elements derived from tolerant donors were capable of transferring the tolerance to naive recipients. Moreover, lymphoid cells obtained from orally tolerant donors exhibited a marked decrease in their capacity to transfer EAE to naive recipient rats, even after in vitro activation with MBP or Con A. We observed that EAE could be readily transferred into orally tolerant rats using MBP-specific encephalitogenic T cell lines. In vitro cell mixing studies showed that the proliferation of lymphocytes from MBP-sensitized donors was not inhibited by the addition of lymphoid cells from tolerant donors, arguing against the role of a suppressor cell. Investigation of MBP-stimulated lymphokine production showed that both IL-2 and IFN-gamma levels were substantially decreased in spleen and lymph node cell cultures from MBP-fed rats compared to vehicle-fed control animals. Furthermore, limiting dilution analyses revealed that MBP-fed rats exhibited a profound decrease in MBP-reactive, IL-2-secreting lymphocytes relative to control animals. Thus, because lymphocytes from MBP-fed rats neither proliferate nor secrete IL-2 or IFN-gamma in response to MBP and we can find no compelling evidence for the role of suppressor cells, we propose that the oral administration of MBP results in a state of clonal anergy.
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PMID:Oral tolerance in experimental autoimmune encephalomyelitis. III. Evidence for clonal anergy. 171 50

The immunomodulatory action of corticosteroids and the ability of central noradrenergic systems to activate the hypothalamic-pituitary-adrenal (HPA) axis led us to investigate the relationship between neuroendocrine status and the clinical course of encephalomyelitis (EAE) following adrenalectomy and depletion of noradrenaline (NA) centrally or peripherally. A significant inverse correlation was found between hypothalamic NA and serum corticosterone (CS) at peak clinical signs of EAE in all the sham groups or when NA was depleted only in the peripheral nervous system. A positive correlation was found between serum CS and disease severity, and in all experimental groups with intact peripheral and/or central noradrenergic pathways a uniformly increased splenic NA content was also observed at peak disease. Administration of 6-OHDA i.p. to neonatal or adult Lewis rats produced a significant depletion of splenic NA alone which resulted in increased disease severity, despite the fact that circulating CS was elevated. Thus the rise in the NA content of lymphoid tissue at peak clinical signs contributes to recovery. A single i.c.v. injection of 6-OHDA into the hypothalamic region resulted in an 80% reduction in NA content, which subsequently modified the clinical severity of EAE. Serum CS levels rose preclinically in the treated group and remained high despite milder clinical disease than that seen in the sham group. The overriding immunoregulatory influence of glucocorticoids is demonstrated by the rapid onset of clinical EAE and morbidity in adrenalectomized animals. However, the strong inverse correlation found between hypothalamic NA and circulating CS indicates that regulation of the HPA axis may ultimately be controlled by central sympathetic pathways.
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PMID:Hypothalamic noradrenergic pathways exert an influence on neuroendocrine and clinical status in experimental autoimmune encephalomyelitis. 177 27

The effectiveness and the mechanism of T cell vaccination were studied in two experimental models of autoimmune disease. The attempt to modulate autoimmune disease via idiotypic regulation of autoreactive antigen-specific T cells was first shown in the rat experimental autoimmune encephalomyelitis (EAE) model where inactivated EAE-inducing T cells could both immunize and protect rats from EAE. We previously reported that low dose T cell vaccination against EAE in Lewis rats was immunologically specific, long lasting and extremely efficient in preventing adoptive transfer of the disease. In experimental autoimmune uveitis (EAU) T cell vaccination was also found to be effective. In both cases, antigen or mitogen activation of the T cells prior to inoculation was required. In the EAE model, T cell vaccination appeared to be associated with two sets of T lymphocytes (CD4+ CD8- helper and CD4- CD8+ cytotoxic/suppressor cells) which were cloned and found to be specifically reactive to the vaccine cells. These anti-idiotypic T cell clones were able to antagonistically modulate the in vitro proliferation of encephalitogenic Z1a cells. In vivo, transfer of the lymph node cells (from which the anti-idiotypic clones were derived) from vaccinated animals to naive syngeneic recipients conferred resistance to EAE. In the EAU model, we also found a consistent immunological response raised against different activated T cells (four T cell lines with irrelevant specificities and mitogen-activated lymphoid cells) in addition to the anti-idiotypic cells. This response, apparently directed to T cell activation markers, might combine with the anti-idiotypic response to regulate autoimmunity.
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PMID:T cell vaccination in autoimmune diseases. 179 4

The expression of two vascular addressins, adhesion molecules implicated in lymphocyte traffic via high endothelial venules (HEV) within lymph node and mucosal tissues, and of an HEV differentiation antigen (Ag) has been followed immunocytochemically in the central nervous system (CNS) of SJL mice at different stages of adoptively-transferred, chronic relapsing experimental autoimmune encephalomyelitis (EAE). Monoclonal antibody (mAb), MECA-325, which defines an HEV cell differentiation Ag generally associated with vessels involved in lymphocyte traffic, gave consistently high levels of expression on and around blood vessels within spinal cord lesions during periods of inflammation (acute onset and relapses). Two mAbs, MECA-89 and MECA-367, both recognizing the same mucosal addressin showed an affinity for endothelial cells and some astrocytes but only in lesions from animals displaying relapses. MECA-79, an mAb against a peripheral lymph node vascular addressin, showed no CNS staining whatsoever. All four antibodies gave uniformly positive staining on control lymphoid tissue. Since some stages of EAE appeared to be associated with the expression of different addressins, the possibility of separate roles for these distinct molecules should be considered.
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PMID:Relapsing autoimmune demyelination: a role for vascular addressins. 195 71

Immune abnormalities, including deficient CD8 lymphocyte-mediated suppression, have been implicated in the progression of multiple sclerosis (MS). The peripheral sympathetic branch of the autonomic nervous system innervates the lymphoid organs and affects immune function. Animals with an ablated sympathetic nervous system develop more severe experimental allergic encephalomyelitis than control animals and exhibit an increased density of beta-adrenergic receptors on their lymphocytes. Experimental allergic encephalomyelitis shares many features with MS. Accordingly, we investigated the psychogalvanic skin reflex in patients with rapidly progressive MS and found that 13 patients (57%) lacked this sympathetic-mediated response. The density of beta-adrenergic receptors on lymphocyte subsets was increased in progressive MS, most notably on the CD8 suppressor/cytotoxic subset. B lymphocytes had the greatest number of receptors with 12.1 +/- 1.8 fmol/10(6) cells in control subjects and 18.7 +/- 2.6 fmol/10(6) cells in patients with MS. CD8 lymphocytes possessed an intermediate number of receptors with 3.4 +/- 0.4 fmol/10(6) cells in control subjects and 9.1 +/- 1.6 fmol/10(6) cells in patients with MS. CD4 lymphocytes demonstrated the fewest receptors with 1.2 +/- 0.1 fmol/10(6) cells in control subjects and 1.8 +/- 0.4 fmol/10(6) cells in patients with MS. No differences in the affinity or function (cyclic adenosine monophosphate levels in response to 10(-5) M (-)isoproterenol) of the adrenergic receptor were found when patients with progressive MS and control subjects were compared. Autonomic abnormalities in progressive MS and the increased beta-adrenergic receptor density found on CD8 lymphocytes may be related.
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PMID:Sympathetic skin responses are decreased and lymphocyte beta-adrenergic receptors are increased in progressive multiple sclerosis. 216 44

Experimental allergic encephalomyelitis (EAE) was induced in Lewis rats using several different immunization protocols, and draining lymph node cells from these animals were assayed for proliferation against heterologous, homologous, and syngeneic MBP, and syngeneic spinal cord. Proliferative responses were largely stimulated by nonsyngeneic antigenic determinants and correlated better with the antigen used to induce EAE than with signs of autoimmune disease. Lymph node cells from rats immunized with either guinea pig spinal cord or syngeneic MBP did not proliferate measurably when restimulated in vitro with syngeneic MBP, yet lymphoid cells from these animals were enhanced in their capacity to transfer EAE following in vitro stimulation with syngeneic MBP.
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PMID:Experimental allergic encephalomyelitis: clinical disease and enhanced cellular transfer in the absence of lymphocyte proliferative responses against syngeneic MBP. 242 18

Experimental allergic encephalomyelitis (EAE) is an animal model of T cell-mediated, central nervous system neuropathology that may be a relevant animal model for multiple sclerosis. EAE is usually induced by sensitization of animals with a xenogeneic myelin basic protein (MBP). Recently, MBP-reactive T cell lines and clones derived from lymphoid tissue of animals with EAE have proved very useful in elucidating certain aspects of the pathogenesis in EAE. However, questions relating to how T cells actually mediate the pathologic changes seen in EAE remain unresolved. We now report for the first time the derivation of long-term, interleukin 2-dependent T cell lines and sublines from a site of pathology in murine EAE--the spinal cord. All of the spinal cord-derived T cell lines and sublines were found to be "autoreactive" in that they responded to self (murine) MBP as well as to the xenogeneic immunogen, porcine MBP. The ability to derive T cell lines and sublines from the spinal cords of mice with EAE should now aid in the elucidation of pathogenetic mechanisms in EAE by allowing for a characterization of those T cells found at the site of pathology.
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PMID:T cell lines derived from the spinal cords of mice with experimental allergic encephalomyelitis are self reactive. 242 82

Gangliosides have been shown to suppress human and murine lymphocyte proliferative responses in vitro. We tested the suppressive effects of gangliosides on the proliferation of autoreactive lymphoid cells obtained from Lewis rats with experimental allergic encephalomyelitis (EAE). Exogenous rat brain gangliosides inhibited both antigen- and mitogen-induced proliferation by as much as 79 and 93%, respectively. Gangliosides similarly inhibited the antigen-induced proliferation of a myelin basic protein (MBP)-reactive T-cell line which is able to passively induce EAE. Suppression was greatest when gangliosides were added at the initiation of culture, and was not abrogated by supraoptimal antigen concentration. Interleukin 2 (IL-2) activity in culture supernatants was not diminished by the addition of gangliosides. Gangliosides did not inhibit the IL-2-induced proliferation of a murine IL-2-dependent cell line, CTLL-20, unless the IL-2 was first preincubated with gangliosides before the addition of CTLL-20. Preincubation of CTLL-20 with gangliosides resulted in no inhibition of the subsequent responses to IL-2. Exogenous gangliosides did not decrease the binding of a monoclonal antibody directed against the rat cell surface IL-2 receptor. Addition of exogenous IL-2 to ganglioside-suppressed cultures had no effect or only partially restored the proliferative responses. Therefore, gangliosides were shown to inhibit the proliferation of autoreactive lymphoid cells without affecting IL-2 production or IL-2 receptor expression.
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PMID:Gangliosides suppress the proliferation of autoreactive cells in experimental allergic encephalomyelitis: ganglioside effects on IL-2 activity. 243 55


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