TGF-beta1-conditioned glial cell-derived dendritic cells inhibit expansion of MBP-reactive T cells in vitro.

Resident microglial cells contribute to activation and expansion of T cells under inflammatory conditions within the CNS. However, there is no evidence how interactions between microglia and T cells affect CNS inflammation. We evaluated the effect of glial cell-derived dendritic cells (GC-DC) in expanding and eliminating myelin basic protein (MBP)-reactive T cells. GC-DC untreated with TGF-beta1 (GC-DC0) primed antigen specific T cell proliferation, whereas GC-DC treated with TGF-1 (GC-DCbeta) effectively inhibited expansion of T cells via inducing IFN-y-expressing CD8+ T cells. Augmented IFN-gamma and/orTNF-alpha might also affect the elimination of MBP-reactive T cells. These results indicate that TGF-beta1-mediated functional skewing of GC-DC plays a critical role for the elimination of MBP-reactive T cells.