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

We next investigated whether the mononuclear cells isolated from the CNS of MBP TCR transgenic mice could actively suppress the responses of T cells isolated from the periphery of the same mice that have not undergone tolerance induction. In control experiments, LN T cells (2 Ï« 10 4 ) from MBP TCR1 or TCR2 transgenic mice were cultured with and without MBP peptide and either irradi- ated APCs alone or with irradiated APCs and CNS cells isolated from 15 to 17 nontransgenic mice. The transgenic LN T cells proliferated strongly to MBP Ac1-11 in both the presence and absence of CNS mononuclear cells isolated from nontransgenic mice (Fig. 5) . These results confirm our observations made with the TEa and DO11.10 TCR transgenic mice that CNS mononuclear cells do not generally suppress T cell proliferation. Interestingly, CNS cells isolated from MBP TCR transgenic mice had a very different effect in these experiments. Proliferation of MBPspecific LN T cells was significantly inhibited upon incubation with CNS cells isolated from MBP TCR transgenic mice compared with incubation with peptide and irradiated APCs alone (Fig. 5, P Ï­ 0.004) . These data are the results of four independent experiments using CNS cells from MBP TCR transgenic mice. Thus, mononuclear cells present only in MBP TCR transgenic mice and not nontransgenic mice are capable of mediating bystander suppression of nontolerant MBP-specific peripheral T cells.