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

T Cells in the CNS of Young TCR Transgenic Mice Are Predominantly Naive. Previous studies in nontransgenic mice indicated that only activated T cells cross the blood-brain barrier (7, 9, 10) . To investigate whether the T cells found in the CNS of TCR transgenic mice also display an activated phenotype, T cell populations in 4-7-wk-old nontransgenic (controls) and Rag Ϫ / Ϫ MBP TCR transgenic mice were analyzed using antibodies specific for cell-surface activation/memory markers. In nontransgenic mice, the majority of CNS T cells expressed high levels of CD44 as well as low levels of CD45RB (Fig. 2 ) and high levels of CD49d (data not shown), consistent with an activated/ memory phenotype. Peripheral T cells from nontransgenic mice expressed significantly lower levels of these activa- tion/memory markers compared with CNS T cells ( P ϭ 0.002). These observations are consistent with earlier studies showing that the CNS is preferentially trafficked by activated T cells.