HIGH-INCIDENCE OF SPONTANEOUS AUTOIMMUNE ENCEPHALOMYELITIS IN IMMUNODEFICIENT ANTIMYELIN BASIC-PROTEIN T-CELL RECEPTOR TRANSGENIC MICE

We have generated TCR transgenic mice (T/R(+)) specific for myelin bas ic protein (MBP) and crossed them to RAG-1-deficient mice to obtain mi ce (T/R(-)) that have T cells expressing the transgenic TCR but no oth er lymphocytes. Both T/R(+) and T/R(-) mice carry, in the lymph nodes and spleen, large numbers of the potentially encephalitogenic CD4(+) a nti-MBP T cells. These cells respond to MBP in vitro but show no signs of activation in vivo. Nevertheless, similar to 14% of H-2(u) T/R(+) and 100% of H-2(u) T/R(-) mice developed spontaneous experimental auto immune encephalomyelitis (EAE) within 12 months. These data indicate t hat EAE can be mediated by CD4(+) anti-MBP T cells in the absence of a ny other lymphocytes and that nontransgenic lymphocytes that are prese nt in T/R(+) but absent in T/R(-) mice have a protective effect. The d ata also suggest that spontaneous EAE may be triggered by an in situ a ctivation of CD4(+) anti-MBP cells in the nervous system.