Expansion and function of CD8+ T cells, expressing Ly49 inhibitory receptors specific for MHC class I molecules

MHC class I-specific Ly49 inhibitory receptors regulate NK cell activation, thereby preventing autologous damage to normal cells. Ly49 receptors are also expressed on a subset of CD8(+) T cells whose origin and function remain unknown. We report here that, despite their phenotypic and cytolytic similarities, Ly49(+)CD8(+) T cells and conventional Ly49(-)CD44(high) memory-phenotype CD8(+) T cells present strikingly distinct features. First, under steady state conditions Ly49(+)CD8(+) T cells are poor cytokine producers (TNF-alpha and IFN-gamma) upon TCR triggering. Second, Ly49(+)CD8(+) T cells are not induced upon various settings of Ag immunization or microbial challenge. However, Ly49 can be induced on a fraction of self-specific CD8(+) T cells if CD4(+) T cells are present. Finally, the size of the Ly49(+)CD8(+) T cell subset is selectively reduced in the absence of STAT1. These results indicate that Ly49 expression is associated with a differentiation program of cytolytic CD8(+) T cells triggered upon chronic antigenic exposure. They further suggest that the size of the Ly49(+)CD8(+) T cell subset marks a history of CD8(+) T cell activation that might preferentially result from endogenous inducers of inflammation rather than from microbial infections.