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)

Experimental autoimmunity of the CNS has been well characterized--the antigen has been identified, effector cell specificity has been defined, and the relationship between cellular sensitization and antibody production has been partially clarified. In the guinea pig, experimental allergic encephalomyelitis (EAE) is induced by one injection of myelin basic protein in complete Freund's adjuvant (BP/CFA). If BP/CFA is preceded by repeated injections of basic protein in incomplete Freund's adjuvant (BP/IFA), EAE is not induced; the guinea pigs survive and ultimately produce antibody. Induction and prevention of EAE as well as antibody induction by this schedule are dependent on the presence of the intact encephalitogenic (T-cell) site in the polypeptide used for sensitization and preimmunization. In contrast, B cell sites (those peptide sequences which bind antibody) are independent of the T-cell site. At least 5 specific antigenic regions (B-cell sites) have been demonstrated in the BP molecule. High mycobacteria levels bypass the specificity requirement of helper T-cells but cannot bypass the specificity requirement of effector T-cells. In spite of the sophisticated immunologic techniques available, our knowledge of humoral and cellular sensitivity in multiple sclerosis (MS) patients is very limited. The experimental demonstration of an analogy between EAE and MS is weak: a) Demonstration of BP-sensitized cells or BP-specific antibodies in peripheral blood of MS patients has not been successful. b) Anti-myelin serum factors reported to be associated with both disease states (experimental autoimmunity and MS) are clearly not identical. Nevertheless, successful treatment of EAE in animals by BP/IFA injections has encouraged consideration of clinical trials to test the therapeutic value of BP injections in MS patients. If successful, the question will be answered: if unsuccessful, the dilemma still remains.
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PMID:Autoimmunity in multiple slcerosis: do we have an experimental model? 8 Sep 41

The efficacy of antigen-specific immunoregulation as a treatment for the efferent limb of an autoimmune disease was tested in a rat model of adoptive experimental autoimmune encephalomyelitis (EAE). Lewis rats receiving 4-5 x 10(7) guinea pig (GP) myelin basic protein (MBP)-activated lymph node T cell blasts from GPMBP/CFA sensitized donors routinely show clinical signs of disease 5-6 days post transfer. Intravenous injection of GPMBP coupled to syngeneic splenocytes using the chemical cross-linker carbodiimide was effective in completely abrogating the expression of clinical EAE in rats that received MBP-specific T cells 2 days previously. Partial inhibition was also observed in rats injected as early as day 0 (the same day as MBP-specific T cell transfer) and as late as 1 day prior to the onset of clinical signs (days 4-5 post transfer). Unresponsiveness was shown to be dose-dependent, dependent on the route of injection of the neuroantigen-coupled splenocytes, and was antigen-specific. Splenocytes coupled with GP or rat MBP (which are identical within the major encephalitogenic GP68-86 Lewis rat determinant with the exception of the residue at position 80) were equally efficient at eliminating disease expression in recipients of GPMBP-specific T cells. In contrast, splenocytes coupled with bovine or rabbit MBP (which differ significantly from GPMBP within the 68-86 region) had no inhibitory effect. The antigen specificity of the tolerance induction was also illustrated by the fact that splenocytes coupled with GP68-86, but not those coupled with the truncated GP68-84 peptide, induced profound unresponsiveness. Interestingly, de novo antigen processing by the antigen-coupled cells did not appear to be necessary as the inclusion of antigen processing inhibitors had no effect on inhibition of disease. However, the use of the carbodiimide coupling reagent was critical for the induction of unresponsiveness as essentially equivalent amounts of 125I-labelled MBP were bound in its presence or absence, but only splenocytes incubated in the presence of both MBP and carbodiimide inhibited clinical expression of disease. Antigen-specific tolerance is thus an effective means of inhibiting expression of clinical disease in the rat EAE model, and a powerful tool for determining the fine epitope specificity of encephalitogenic T cells.
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PMID:Antigen-specific inhibition of the adoptive transfer of experimental autoimmune encephalomyelitis in Lewis rats. 137 53

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory neurological disease initiated by activated T cells specific for the autoantigen, myelin basic protein (MBP). The ability of Lewis rat splenic T cells to transfer EAE after in vitro incubation with MBP-pulsed dendritic cells (DC) was used as an index of MBP-specific T cell activation. OVA, previously processed by macrophages, was incubated with MBP and DC at the pulsing stage to determine whether it could inhibit presentation of the autoantigen. At molar equivalents of 2.5:1 and 20:1 relative to MBP, processed OVA increasingly inhibited the ability of DC to activate MBP-specific T cells for EAE transfer. Unprocessed OVA, which cannot be presented immunogenically by Lewis rat DC, was much less effective. However, processed OVA added to DC after they had been pulsed with MBP could not compete. OVA also blocked appearance of EAE when mixed with MBP/CFA in the inoculum used for active induction of the disease. Splenic T cells from MBP + OVA/CFA-immunized rats transferred EAE with a substantially delayed onset, suggesting that a reduced number of MBP-specific T cells was generated by immunizing with the OVA + MBP mixture compared with MBP alone. Overall, the data indicate that fragments of a foreign protein, OVA, which can be bound by APC, can also inhibit presentation of encephalitogenic determinants of MBP to T cells.
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PMID:Competition between foreign and self proteins in antigen presentation. Ovalbumin can inhibit activation of myelin basic protein-specific T cells. 168 45

Chronic-relapsing experimental allergic encephalomyelitis (CR-EAE) in the Lewis rat, induced by the injection of spinal cord tissue in complete Freund's adjuvant (SC/CFA), was studied in vivo by treatment with liposomes containing central nervous tissue antigens, and in vitro by lymphocyte proliferation assays. Intracardiac administration of myelin basic protein (MBP) liposomes, galactocerebroside (GC) liposomes, or MBP + GC liposomes substantially reduced the clinical severity and/or delayed the onset of the initial phase of disease. Liposomes prepared from whole myelin provided even greater protection, and were effective at suppressing both the first disease episode and the relapses. These results indicate that while GC and MBP may play significant roles in the development of CR-EAE in the Lewis rat, immune responses to other antigens are probably also involved. Splenic and lymph node lymphocytes from MBP-GC liposome-treated rats, and splenic lymphocytes from cytochrome-GC (CYT-GC) liposome-treated rats, showed drastically reduced abilities to proliferate in response to MBP in culture. Spleen cells from both the MBP-GC- and CYT-GC-liposome-treated donors were able to actively suppress antigen-induced proliferation of MBP-primed lymphocytes. These findings suggest participation of both clonal anergy, and active suppressor cells in the liposome-mediated suppression of CR-EAE in the Lewis rat.
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PMID:Treatment of spinal cord-induced experimental allergic encephalomyelitis in the Lewis rat with liposomes presenting central nervous system antigens. 169 33

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

The LOU/M rat (RT-1w) haplotype, although resistant to an encephalitogenic challenge of guinea pig myelin basic protein (Gp-BP)/CFA and unresponsive to Gp-BP, responded strongly to human (Hu)-BP. Both T cell and antibody responses focused on the 110-129 determinant of Hu-BP, and T cells specific for this epitope transferred clinical and histologic experimental autoimmune encephalomyelitis (EAE) to naive LOU/M rats. Moreover, EAE could be induced actively with Hu-BP and a synthetic Hu-S110-129 peptide in CFA, but only with co-immunomodulation by pertussis toxin or cyclophosphamide. Analysis of TCR V region genes revealed the predominant use of the V beta 8.5-J beta 2.3 gene combination, with extensive N region additions to both D beta 1 and D beta 2. These results define the Hu-BP 110-129 peptide sequence as the major encephalitogenic epitope for the LOU/M strain of rat previously considered resistant to EAE, and support the idea that the encephalitogenic property of BP and other CNS Ag for a given MHC is encompassed within immunodominant T cell epitopes. Furthermore, the TCR sequence data indicate the predominant use of a different V beta 8 subfamily member (V beta 8.5) than the V beta 8.2 gene used preferentially by several other rat strains and the PL/J mouse in the T cell response to BP.
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PMID:T cell lines specific for an immunodominant epitope of human basic protein define an encephalitogenic determinant for experimental autoimmune encephalomyelitis-resistant LOU/M rats. 170 3

Protease-containing supernatants from activated rat mast cells were found to degrade purified rat myelin with a subsequent release of a stable encephalitogenic peptide. The two most abundant peptides were identified as residues 69-87 (GSLPQKSQRTQDENPVV) and residues 69-88 (GSLPQKSQRTQDENPVVH). While additional exposure to the mast cell supernatants removes the COOH terminal histamine from peptide 69-88 to yield peptide 69-87, additional proteolytic degradation of the 69-87 peptide was not detected. Immunization with this peptide emulsified in CFA caused the development of clinical experimental autoimmune encephalomyelitis (EAE) in Lewis rats. In addition this 69-87 sequence was found to activate resting encephalitogenic myelin basic protein-reactive T cell lines to adoptively transfer clinical EAE. The release of stable encephalitogenic peptides from the myelin sheath by mast cell proteases may play a role in activation of encephalitogen-specific T cells during the progression of EAE.
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PMID:Mast cell proteases liberate stable encephalitogenic fragments from intact myelin. 170 29

The effects of Neurotropin, a substance extracted from the inflammatory dermis of rabbits inoculated with Vaccinia virus, for experimental allergic encephalomyelitis (EAE) in Lewis rats, a model for human multiple sclerosis (MS), was studied. The peptide defined by residues 68-84 (MB 68-84) which corresponds to the encephalitogenic portion of the guinea pig myelin basic protein (MBP) in complete adjuvant H37Ra (CFA) was injected into the hind foot pad of each rat. Neurotropin significantly suppressed the clinical and histological expression of actively induced EAE when administered i.p. daily from day 0 to day 6 after immunization. In addition, passive EAE induced by precultured spleen cells from rats immunized with MB 68-84 in CFA was also suppressed by daily administration of Neurotropin after cell transfer. Neurotropin treatment significantly suppressed the delayed-type hypersensitivity (DTH) response to MB 68-84. Furthermore, the ability of spleen cells from Neurotropin-treated rats to transfer EAE was significantly lower than that of saline-treated rats. It seemed that the suppression may be due to the inhibition of the activation by MB 68-84 of sensitized spleen cells, as demonstrated by proliferative response to MB 68-84. However, no difference was observed in Con A-induced proliferative response of the spleen cells between Neurotropin- and saline-treated rats. These findings indicate that Neurotropin inhibits EAE by suppressing the immune responses to encephalitogenic MBP with little non-specific suppression.
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PMID:Neurotropin inhibits experimental allergic encephalomyelitis (EAE) in Lewis rats. 171 61

To assess the role of IL-1 in the development of experimental autoimmune encephalomyelitis (EAE), the effects of in vivo treatment with IL-1 alpha or an IL-1 antagonist on the clinical course of EAE were evaluated. First, Lewis rats were immunized with guinea pig myelin in CFA and treated for 19 consecutive days with i.p. injections of recombinant human IL-1 alpha. Clinical signs of paralysis in the IL-1 alpha-treated groups were of longer duration and of greater severity compared to placebo injected controls. In addition, more weight loss was observed in the IL-1 alpha-treated groups compared to controls. This enhanced weight loss was not due to IL-1 alpha injections alone as CFA-treated rats injected with IL-1 alpha did not lose weight when compared to placebo injected, CFA-treated controls. Second, soluble mouse rIL-1R (sIL-1R), which binds both IL-1 alpha and IL-1 beta, was given as an IL-1 antagonist. Treatment of guinea pig myelin/CFA immunized rats with sIL-1R for 13 consecutive days significantly delayed the onset of EAE, reduced the severity of paralysis and weight loss, and shortened the duration of disease. Treatment with sIL-1R was most effective in reducing EAE if administered for 15 consecutive days immediately after immunization. Shortened 5-day treatment regimens spanning days 1 to 5, days 6 to 10, or days 11 to 15 after immunization were less effective in reducing EAE. These data suggest that IL-1 may initiate or promote inflammation within the central nervous system. In addition, specifically blocking the biological activity of IL-1 in vivo by soluble receptors may prove beneficial for the treatment of autoimmune or inflammatory diseases.
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PMID:Experimental autoimmune encephalomyelitis is exacerbated by IL-1 alpha and suppressed by soluble IL-1 receptor. 182 2


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