B cells directly tolerize CD8(+) T cells

This report investigates the response of CD8(+) T cells to antigens present ed by B cells. When C57BL/6 mice were injected with syngeneic B cells coate d with the K-b-restricted ovalbumin (OVA) determinant OVA(257-264), OVA-spe cific cytotoxic T lymphocyte (CTL) tolerance was observed. To investigate t he mechanism of tolerance induction, in vitro-activated CD8+ T cells from t he K-b-restricted, OVA-specific T cell receptor transgenic line OT-I (OT-I cells) were cultured for 15 h with antigen-bearing B cells, and their survi val was determined. Antigen recognition led to the killing of the B cells a nd, surprisingly, to the death of a large proportion of the OT-I CTLs. T ce ll death involved Fas (CD95), since OT-I cells deficient ill CD95 molecules showed preferential survival after recognition of antigen on B cells. To i nvestigate the tolerance mechanism in vivo, naive OT-I T cells were adoptiv ely transferred into normal mice, and these mice were coinjected with antig en-bearing B cells. In this case, OT-I cells proliferated transiently and w ere then lost from the secondary lymphoid compartment. These data provide t he first demonstration that B cells can directly tolerize CD8(+) T cells, a nd suggest that this occurs via CD95-mediated, activation-induced deletion.