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

The increased ability of activated/memory T cells to cross the blood-brain barrier may explain our finding in nontransgenic mice that more CD8 Ï© T cells are found within the CNS than CD4 Ï© T cells. In the periphery of nontransgenic mice, the activated/memory T cell population contains a greater percentage of CD8 Ï© than CD4 Ï© T cells. The CD44 high T cell population in the periphery has been shown to have a higher percentage of CD8 Ï© T cells relative to CD4 Ï© T cells in other models as well (32) . Alternatively, experiments in a different system suggest that CD8 Ï© T cells may preferentially traffic through the CNS (33) . In these studies, dendritic cells and moth-cytochrome C peptide were injected into the CSF of MHC class IIrestricted moth-cytochrome C peptide TCR transgenic mice. Preferential recruitment of MHC class I-restricted cells to the CNS was observed even though MHC class II molecules presented the stimulating antigen. These findings and our results are both consistent with enhanced re-circulation or accumulation of CD8 Ï© T cells through the CNS.