Altered effector responses of H-Y transgenic CD8(+) cells

The primary role of CD8(+) T cells is to destroy virus-infected or tumor cells expressing cognate antigens in the form of peptide-MHC class I complexes. This destruction is primarily achieved by the actions of lytic mediators and/or lymphokines. In this report, we show that mature, H-Y/D-b-specific CD8(+) T cells from H-Y TCR transgenic mice were unable to efficiently release lytic mediators after antigenic stimulation, However, anti-TCR antibody induced granule exocytosis and target cell lysis, arguing against signaling and/or cytolytic machinery defects in CD8(+) cells, and demonstrating that male antigen induced differentiation of 'naive' into effector CD8(+) cells, Stimulation of H-Y-specific effector CD8(+) T cells with male stimulators, although insufficient to induce lytic granule release, was sufficient for H-Y-specific IFN-gamma production, Unexpectedly, this effector-phase IFN-gamma production was dependent on B7-2 engagement, We hypothesize that altered effector functions in H-Y-specific CD8(+) cells are due to the low affinity of TCR-antigen-MHC interaction and/or the elevated threshold of CD8(+) T cell activation.