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

To investigate the mechanism of tolerance induction in the CNS, we first determined if the MBP-specific T cells isolated from the CNS were anergic. CNS T cells from both MBP TCR1 and MBP TCR2 transgenic mice were harvested and stimulated with MBP Ac1-11 and irradiated APCs in the presence and absence of IL-2. CNS T cells isolated from both transgenic models remained nonresponsive to antigen even in the presence of IL-2, whereas LN T cells from the same mice proliferated robustly (data not shown). Therefore, the lack of proliferation observed with MBP-specific T cells from the CNS was not due to an ability to produce IL-2. In all experiments described so far, no more than 21 MBP TCR transgenic mice were pooled per experiment. In one additional experiment, 36 MBP TCR1 TCR transgenic mice were pooled in order to expand the number of wells exposed to IL-2. In this experiment, both CNS and LN T cells proliferated in the presence and absence of IL-2 (data not shown). No proliferation was detected in any of the other experiments using MBP TCR transgenic CNS T cells (n Ï­ 5). Therefore, we suspect that the unusually large number of mice pooled in this experiment included a mouse with subclinical EAE. The incidence of spontaneous EAE in the colony from which these mice were obtained is 15%. T cells in the CNS of mice with subclinical EAE will already be activated and would be expected to proliferate in vitro.