ENCEPHALITOGENIC T-CELLS ARE PRESENT IN LEWIS RATS PROTECTED FROM AUTOIMMUNE ENCEPHALOMYELITIS BY COIMMUNIZATION WITH MBP73-84 AND ITS ANALOG

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory dis ease of the central nervous system (CNS) that is mediated by T helper 1 (Th1) CD4(+) T cells, Lewis rats can be protected from actively indu ced EAE by coimmunization with the encephalitogenic myelin basic prote in (MBP) epitope 73-84 and its single alanine-substituted analog 1028, Although analog 1028 cannot induce either active or passive EAE, it d oes elicit a Th1-like response that is crossreactive with MBP73-84. An alog 1028 can effectively inhibit clinical EAE in a dose-dependent man ner when rats are coimmunized with the encephalitogenic peptide MBP73- 84 and 1028 in complete Freund adjuvant (CFA). Stimulation of cells fr om MBP73-84:1028-coimmunized protected rats proliferate and secrete in terferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in vitro in response to MBP73-84. Furthermore, coimmunized protected rats harbor a population of MBP73-84-reactive potentially encephalitog enic T cells, because splenocytes from these rats can be stimulated to transfer passive EAE to naive recipients, Thus, the protection of coi mmunized rats by analog 1028 is not due to the inhibition of priming o f MBP73-84-reactive T cells or alteration of the cytokine secretion pr ofile of the MBP73-84-reactive cell population, Rather, MBP73-84-react ive potentially encephalitogenic T cells are primed in these protected animals. (C) 1996 Wiley-Liss, Inc.