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

Previous studies of T cell tolerance to tissue-specific antigens indicated that tolerance occurred in LNs draining the relevant tissue. For example, T cells specific for antigens expressed in the pancreas undergo deletion within the LNs draining the pancreas (34) (35) (36) (37) (38) . In contrast, we demonstrate that induction of tolerance in MBP-specific T cells occurs within the target organ itself rather than within a lymphoid tissue. First, we confirmed that our CNS T cell isolation procedures from MBP TCR transgenic mice produced T cells that were present behind the blood-brain barrier in vivo without significant contamination of peripheral T cells (see Materials and Methods). Second, we examined T cells isolated from cervical LNs for evidence of tolerance because these LNs are believed to drain the CNS (29, 30) .