High incidence of spontaneous autoimmune encephalomyelitis in immunodeficient anti-myelin basic protein T cell receptor transgenic mice

Abstract

We have generated TCR transgenic mice ( T R + ) specific for myelin basic protein (MBP) and crossed them to RAG-1-deficient mice to obtain mice ( T R − ) that have T cells expressing the transgenic TCR but no other lymphocytes. Both T R + and T R − mice carry, in the lymph nodes and spleen, large numbers of the potentially encephalitogenic CD4 + anti-MBP T cells. These cells respond to MBP in vitro but show no signs of activation in vivo. Nevertheless, ∼ 14% of H-2 u T R + and 100% of H-2 u T R − mice developed spontaneous experimental autoimmune encephalomyelitis (EAE) within 12 months. These data indicate that EAE can be mediated by CD4 + anti-MBP T cells in the absence of any other lymphocytes and that nontransgenic lymphocytes that are present in T R + but absent in T R − mice have a protective effect. The data also suggest that spontaneous EAE may be triggered by an in situ activation of CD4 + anti-MBP cells in the nervous system.