[Experimental allergic encephalomyelitis: immunopathological analysis of antigenic reactivity and loss of...

Experimental allergic encephalomyelitis (EAE) is an autoimmune demyelinating disease of the central nervous system (CNS). EAE can be induced by immunization with myelin basic protein (MBP) or passive transfer of MBP-reactive T cell lines and clones. We established several T-cell clones from SJL/J mice by immunization with whole rat MBP or a synthetic peptide encompassing guinea pig MBP 89-101 which contains the encephalitogenic determinant for SJL/J mice. One clone was found to have lost its encephalitogenicity during long-term passages in vitro, although this clone maintains its specific reactivity to the encephalitogenic determinant. To clarify the difference between the encephalitogenic T cell clone (4b. 14a) and the non-encephalitogenic T-cell clone (4b. 14a/n), we examined the suppressive activity of 4b. 14a/n on the reactivity to antigen of 4b. 14a, various lymphokine production and adhesion molecules expression of 4b. 14a and 4b. 14a/n. The culture fluid of the both 4b. 14a/n and 4b. 14a revealed a suppressive effect on the proliferation of 4b. 14a stimulated by MBP 89-101, and the effect was not different between these clones. In lymphokine production, the activities of lymphotoxin, interferon or interleukin-2 were not different between encephalitogenic clones (4b.14a and TNT-1) and 4b. 14a/n, whereas the activity of tumor necrosis factor-alpha, passively secreted by antigen presenting cell, was higher in culture media of 4b. 14a/n. Examination of adhesion molecule expression of 4b.14a/n failed to show any differences in expression of lymphocyte function-associated antigen-1 (LFA-1) alpha and CD2 in the comparison with 4b. 14a. However, LFA-1 beta expression of 4b. 14a/n was always less than of 4b. 14a. The present studies indicated that the lack of encephalitogenicity of T-cell clones which were responsive to an encephalitogenic determinant depends not on the difference in major lymphokines production but partially on adhesion molecules expression which was decreased in non-encephalitogenic T-cell clone.