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)

To characterize the cellular immune response in an autoimmune lesion, we investigated the accumulation of specific T cells in the central nervous system in actively induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats, using a limiting dilution analysis (LDA) assay for T cells that proliferate in response to antigens. Lymphocytes isolated from the spinal cord infiltrate were compared with cells from the popliteal lymph nodes with respect to frequency of cells responding to basic protein (BP), mycobacterium tuberculosis (MT), the 65-kD heat shock protein (hsp65), allogeneic brown norway spleen cells, and concanavalin A. Additionally, we compared the BP frequency in acute EAE of cells from the spinal cord, peripheral blood, spleen and lymph nodes, and the spinal cord and lymph node after recovery from EAE. We found that acute EAE was associated with marked enrichment of BP-reactive T cells in the spinal cord relative to their frequency in the lymphoid organs and peripheral blood. The infiltrate was also enriched for T cells responding to hsp65; alloreactive T cells, in contrast, were not enriched. The frequency of BP reactive T cells in the spinal cord was highest at the peak of paralysis; however, BP-reactive T cells could still be detected at moderate frequencies after clinical recovery. We established BP- and Mycobacteria-reactive T cell lines from the spinal infiltrates that were CD4+ and TcR alpha beta +. Most of the BP lines were found to react to the major encephalitogenic epitope of guinea pig BP for rats (amino acids 71-90); these lines were found to mediate EAE in naive recipients. T cell lines recognizing other epitopes of BP were not encephalitogenic. All of the lines responsive to Mycobacteria recognized hsp65 or hsp70. These results indicating that the immune infiltrate in active EAE is enriched with cells responding to the autoantigen and to hsp65 were confirmed in EAE adoptively transferred by anti-BP T cell clone.
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PMID:T cells in the lesion of experimental autoimmune encephalomyelitis. Enrichment for reactivities to myelin basic protein and to heat shock proteins. 128 35

We now have substantial evidence demonstrating noradrenergic sympathetic and peptidergic innervation of both primary and secondary lymphoid organs. We have established criteria for norepinephrine, and some of the neuropeptides, as neurotransmitters, and have found changes in immune responsiveness following pharmacological manipulation of noradrenergic sympathetic or peptidergic nerves. Classic receptor binding studies have demonstrated a wide variety of target cells that possess beta-adrenoceptors and receptors for neuropeptides on cells of the immune system, including lymphocyte subsets, macrophages, accessory cells, or stromal elements. In this chapter we describe noradrenergic and peptidergic innervation of primary and secondary lymphoid organs in development, at maturation and during the normal aging process, and discuss possible functional implications of direct neural signals onto cells of the immune system at critical time points in the lifespan of an animal. Further, we examine for involvement of noradrenergic sympathetic and peptidergic innervation in the development and progression of several autoimmune disorders, including adjuvant-induced arthritis, New Zealand mice strains as a model for hemolytic anemia and lupus-like syndrome, and the experimental allergic encephalomyelitis model for multiple sclerosis.
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PMID:Innervation of lymphoid organs and implications in development, aging, and autoimmunity. 131 62

We examined T cells isolated from an autoimmune tissue lesion and from lymphoid organs for their ability to secrete tumor necrosis factor-alpha (TNF-alpha) and to adhere to extracellular matrix (ECM) proteins. CD4+ T cells were obtained from spleens, popliteal lymph nodes, and spinal cords of Lewis rats that had been immunized with myelin basic protein (MBP) to induce experimental autoimmune encephalomyelitis (EAE). We now report that, irrespective of whether or not the T cells were activated with MBP or the T cell mitogen concanavalin A (ConA), the T cells isolated from the spinal cord lesions secreted greater amounts of TNF-alpha and adhered better to ECM than did T cells from the draining lymph node. Thus, the lesions of EAE concentrate a subpopulation of CD4+ T cells with enhanced ability to interact with blood vessel wall components and to secrete TNF-alpha.
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PMID:T cells in the spinal cord in experimental autoimmune encephalomyelitis are matrix adherent and secrete tumor necrosis factor alpha. 137 27

To determine whether there is predominance of T cells expressing a particular TCR V beta chain in the inflammatory lesions of an autoimmune disease model, TCR expression was analyzed in central nervous system (CNS) tissues of mice with experimental allergic encephalomyelitis (EAE). Acute EAE was induced in SJL/J mice either by sensitization with a synthetic peptide corresponding to myelin proteolipid protein residues 139-151 or by adoptive transfer of myelin proteolipid protein peptide 139-151-specific encephalitogenic T cell clones. Mice were killed when they showed clinical signs of EAE or by 40 days after sensitization or T cell transfer. Cryostat CNS and lymphoid tissue sections were immunostained with a panel of mAb to T cell markers and proportions of stained cells were counted in inflammatory foci. In mice with both actively induced and adoptively transferred EAE, infiltrates consisted of many CD3+, TCR alpha beta+, and CD4+ cells, fewer CD8+ cells, and small numbers of TCR gamma delta+ cells. Approximately 30% of CD45+ leukocytes in the inflammatory foci were T cells. Cells expressing TCR V beta 2, 3, 4, 6, 7 and 14 were detected in the infiltrates, whereas TCR V beta 8 and 11, which that are deleted in SJL mice, were absent. When EAE was induced by transfer of T cell clones that use either V beta 2, 6, 10, or 17, there was also a heterogeneous accumulation of T cells in the lesions. Similar proportions of TCR V beta+ and gamma delta+ cells were detected in EAE lesions and in the spleens of the mice. Thus, at the time that clinical signs are present in acute EAE, peripherally derived, heterogeneous TCR V beta+ cells are found in CNS lesions, even when the immune response is initiated to a short peptide Ag or by a T cell clone using a single TCR V beta.
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PMID:The immunopathology of acute experimental allergic encephalomyelitis induced with myelin proteolipid protein. T cell receptors in inflammatory lesions. 138 45

Lymphoid cells from normal and myelin basic protein (MBP)-immune PL/J, SJL/J and (SJL x PL)F1 hybrid mice were activated by in vitro culture with monoclonal antibodies specific for CD3 or specific T cell receptor (TCR) V beta chains. Lymphoid cells activated in this manner from MBP-immune animals did not readily transfer experimental acute encephalomyelitis (EAE) to naive syngeneic recipients in contrast to lymphoid cells from the same source cultured with concanavalin A (ConA) or myelin basic protein (MBP). However, recipients of anti-TCR antibody-activated MBP-specific blasts showed accelerated onset and increased severity of EAE following immunization with MBP as compared to unmanipulated control animals. Anti-TCR activated cells incorporated [3H]-thymidine at a level comparable to ConA or antigen-stimulated cells and secreted interleukin (IL)-2 at comparable levels Anti-TCR activated blasts were greater than 90% positive for CD3 and alpha/beta TCR, 60% CD4+ and 30% CD8+. PL/J or (SJL x PL)F1 recipients of anti-TCR-activated spleen cells from syngeneic normal mice also had more severe EAE than control mice following immunization with MBP. Non-responder C57BL/10SnJ mice could be converted to responders by infusion of anti-CD3 or anti-V beta 8 monoclonal antibody-treated syngeneic spleen cells taken from normal syngeneic unimmunized mice.
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PMID:Experimental allergic encephalomyelitis in susceptible and resistant strains of mice after adoptive transfer of T cells activated by antibodies to the T cell receptor complex. 138 81

This study utilized Lewis rats and the cell-transfer form of experimental allergic encephalomyelitis (EAE) to focus on two central nervous system microvascular alterations known to be intimately associated with early clinical neurological signs of the disease, namely increased vascular permeability and deposition of fibrin. The main objective of the work was to define the degree of concordance and the anatomical localization of maximal vascular permeability change and fibrin deposition within the neuraxis of recipient rats during the earliest expression of clinical manifestations of the disease. Recipients were injected with predetermined doses of activated, myelin basic protein (MBP)-reactive syngeneic donor lymphoid cells and killed 6 or 7 days later when they exhibited the first clinical signs of disease. This experimental design allowed assessment of late occurring immune activities of a single population of MBP-reactive effector cells. Increased vascular permeability, expressed as mean extravascular blood equivalents (EVBE), attained maximum change, i.e., 16.04 +/- 5.07, within the lumbosacrococcygeal segment of the spinal cord (LSC). Maximal density of fibrin depositions, i.e., 192 +/- 94 deposits, also occurred within the LSC cord. The concordance of these two histoimmunopathological events, their tight linkage to early clinical signs of disease and the fact that both events attained maximal values within the LSC cord suggest that increased permeability and activation of the coagulation cascade may be prerequisite events for the expression of neurological signs of EAE.
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PMID:Concordance and localization of maximal vascular permeability change and fibrin deposition in the central neuraxis of Lewis rats with cell-transferred experimental allergic encephalomyelitis. 157 54

SK&F 105685 (N,N-Dimethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2-propanamine+ ++ dihydrochloride) is a novel azaspirane with beneficial activity in animal models of autoimmune diseases such as adjuvant-induced arthritis and experimental autoimmune encephalomyelitis in the Lewis rat and lupus-like disease in the MRL mouse. The effect of SK&F 105685 on the proliferation of rat lymphoid cells was examined in vitro. The compound inhibited the proliferative response of spleen, thymus and lymph node cells to the mitogen concanavalin A (Con A) in a dose-dependent manner but had little or no effect on the mitogenic response of peripheral blood lymphocytes. Although less potent than cyclosporin A, SK&F 105685 was able to inhibit the proliferation of spleen cells stimulated with PMA and ionomycin or the mitogens phytohemagglutinin (PHA), Con A and pokeweed mitogen (PWM). Relatively early event(s) in cell proliferation were affected by SK&F 105685 since delaying addition of the drug by 24 to 48 hours after Con A stimulation of rat spleen cells resulted in reduced levels of suppression. The mode of action of SK&F 105685 appeared to differ from that of cyclosporin A or rapamycin. Unlike cyclosporin A, SK&F 105685 did not affect IL-2 production by Con A-stimulated spleen cells or the IL-2-producing Jurkat cell line, but, like rapamycin, the compound significantly reduced the IL-2-induced proliferation of rat ConA blasts. These results suggest that inhibition of lymphocyte proliferation by SK&F 105685 may require the activity of an intermediate effector cell(s) present in susceptible populations such as cells from the spleen, thymus, lymph nodes and Con A blast preparations but absent or present in low numbers in resistant populations such as peripheral blood cells. Indomethacin and NG-monomethyl-L-arginine (NGMMA), a competitive inhibitor of nitric oxide synthase, were both unable to relieve SK&F 105685-induced suppression of splenic Con A responses thereby ruling out a role for the production of prostaglandins or nitric oxide by macrophages as an intermediate in drug-mediated suppression. In summary, SK&F 105685 was unable to inhibit lymphoproliferative responses by a mechanism distinct from that of cyclosporin A or rapamycin and which appears to involve regulation of cellular interactions rather than a direct effect on responding lymphocytes.
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PMID:Inhibition of lymphoproliferative responses by SK&F 105685, a novel anti-arthritic agent. 166 43

The expression of a battery of adhesion-related molecules and cytokines was investigated by immunocytochemistry in the central nervous system (CNS) of SJL/J mice sensitized for experimental autoimmune encephalomyelitis (EAE). These molecules consisted of the ligands MECA-325, intercellular adhesion molecule-1, and major histocompatibility complex molecules I and II, plus the receptors lymphocyte function-associated antigen-1, CD8, and CD4. The cytokines comprised interferon-gamma and tumor necrosis factor-alpha. EAE was induced by the adoptive transfer of myelin basic protein-sensitized lymphocytes. MECA-325, a marker for murine high endothelial venules in lymph node tissue, was absent from normal CNS tissue, was expressed at low levels on venules 24 to 48 hours before the onset of clinical signs, rose to maximal levels during acute disease, decreased to preclinical levels during remissions, and rose again during relapses. Intercellular adhesion molecule-1, major histocompatibility antigen-I, and major histocompatibility antigen-II showed similar fluctuations around CNS vessels. The receptors lymphocyte function-associated antigen-1 and CD4 fluctuated in parallel with the above molecules, whereas CD8 remained at a similar low level. Interferon-gamma was present during the acute, remitting, and relapsing phases and was localized to inflammatory cells, whereas tumor necrosis factor occurred at low levels only. Thus, several molecules associated with lymphocyte traffic in lymphoid tissue are selectively expressed in a stage-specific manner within the target organ, the CNS, during EAE. This suggests that the CNS may act as an ancillary organ of the immune system, and that cellular traffic into the CNS during EAE is related to the fluctuating expression of several distinct adhesion-related molecules, frequently co-expressed on the same vessel. The findings may have relevance to the sequence of events in the developing CNS lesion of multiple sclerosis.
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PMID:Adhesion-related molecules in the central nervous system. Upregulation correlates with inflammatory cell influx during relapsing experimental autoimmune encephalomyelitis. 167 55

Experimental allergic encephalomyelitis (EAE) effector cells known to exist in guinea pigs with myelin basic protein-incomplete Freund's adjuvant (MBP-IFA)-induced resistance to EAE could be activated in vivo by means of allogeneic confrontation (local host-versus-graft reaction (HVGR)). The abrogation of the resistance was observed only when HVGR was combined with encephalitogenic challenge (myelin basic protein-complete Freund's adjuvant (MBP-CFA)) in a certain order and at certain time intervals. The injection of 20 x 10(7) gamma-irradiated allogeneic lymphoid cells 7 or 4 days prior to or along with MBP-CFA treatment resulted in development of EAE with delayed onset and protracted course. The effect was most prominent when HVGR was induced on day -4. Histological examination revealed inflammatory lymphoid cell infiltrations in spinal cord. Serum level of total and anaphylactic anti-MBP antibodies correlated with the clinical picture.
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PMID:Abrogation of induced resistance to experimental allergic encephalomyelitis in guinea pigs by host-versus-graft reaction. 169 13

The cellular transfer of clinical experimental allergic encephalomyelitis (EAE) with immune spleen cells is only accomplished following lymphoid cell stimulation during an intervening in vitro culture activation period. Recipients of these cells recover from the ensuing adoptively transferred paralytic episode and subsequently respond to active challenge with myelin basic protein (BP)-CFA in an accelerated time frame consistent with the presence of memory cells in the initial cell transfer inoculum. We have found that the addition of anti-CD4 antibody or dexamethasone during the activation period inhibits the development of the transfer active EAE effector cell subpopulation, but does not alter the in vitro development and subsequent expression of the BP-specific memory cell subpopulation. Additional experiments also suggest the development of memory cells in the absence of effector cell activity. PMA + ionomycin when used as a stimulus during the culture activation period leads to effector and memory cell development. The stimulation response is dose dependent, in that a reduced concentration of PMA + ionomycin does not lead to EAE effector cell development; however, at these reduced levels of PMA + ionomycin, memory cell development still occurred. Additional evidence which supports the concept of independent development of memory cells and effector cells was obtained with a BP-specific cell line. Following recovery from cell line-mediated clinical EAE, as well as following adoptive transfer of the cell lines in the precursor stage, cell recipients did not develop an early onset of active EAE when subsequently immunized with BP-CFA. Thus the BP-specific T-cell line appears to contain the precursors of the effector cell subpopulation but does not appear to contain the BP memory cell subpopulation. Collectively these observations suggest the existence of distinct T-cell subsets or pathways of development that are followed during the response to BP as measured by the development of clinical EAE.
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PMID:Adoptive transfer of experimental allergic encephalomyelitis: conditions influencing memory and effector cell development. 169 73


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