In Situ Tolerance within the Central Nervous System as a Mechanism for Preventing Autoimmunity

Brabb, Thea; von Dassow, Peter; Ordonez, Nadia; Schnabel, Bryan; Duke, Blythe; Goverman, Joan

Animals. The high incidence of spontaneous EAE in recombinase activating gene (Rag) Ϫ / Ϫ MBP TCR transgenic mice suggests that T cells may be activated by encountering MBP epitopes in vivo. Activation of MBP-specific T cells within the CNS is only possible if some naive T cells gain access to this tissue. To investigate this possibility, we isolated lymphocytes from the brain and spinal cord of clinically healthy, 4-7-wk-old, well perfused, MBP TCR1 transgenic mice on the Rag ϩ / ϩ background. Lymphocytes from individual animals were analyzed to avoid mixing cells from any mice that had preclinical spontaneous EAE with cells from healthy mice. Surprisingly, the number of T cells per gram of CNS tissue isolated from young, healthy MBP TCR1 transgenic mice was comparable to the number isolated from nontransgenic control mice ( Fig. 1 ). This result was unexpected because entry into the CNS is believed to be limited to activated T cells (7, 9, 10) , and TCR transgenic mice typically have few activated T cells in the periphery (14, 24) .