Loss of CD28 expression on CD8(+) T cells is induced by IL-2 receptor gamma chain signalling cytokines and type IIFN, and increases susceptibility toactivation-induced apoptosis

CD8(+)CD28(-) T cells are selectively expanded during viral infections, ind icating their importance in anti-viral immune responses. Since little is kn own about the differentiation of CD8(+)CD28(-) cells, we investigated the g eneration, function and survival characteristics of this subset. In healthy individuals CD8(+)CD28(-) T cells contained more elevated levels of perfor in and IFN-gamma than the CD8(+)CD28(+) subset, indicating that they can ha ve an effector function. CD8(+)CD28(-) cells were selectively expanded when activated CD8(+)CD28(+) T cells were cultured in IL-2, IL-7 or IL-15, More over, the generation of CD8(+)CD28(-) cells was accelerated by type I IFN s uggesting that these cytokines which are released during viral infections i nfluence CD8(+) T cell differentiation, We did not observe re-expression of CD28 by CD8(+)CD28(-) T cells in any of the experiments performed. Activat ed T cells are susceptible to activation-induced cell death (AICD) if re-st imulated in the absence of co-stimuli. AICD was induced in both CD28(+) and CD28(-) subsets of activated T cells when stimulated with anti-CD3 antibod y in the absence of co-stimuli but the magnitude of death was greater in th e CD28(-) subset. While co-stimulation through LFA-1 (CD11a and CD18) signi ficantly reduced AICD in the CD8(+)CD28(+) subset, death was not prevented in CD8(+)CD28(-) cells. These results suggest that CD8(+)CD28(-) T cells ar e more functionally differentiated than the CD8(+)CD28(+) subset and indica te they may represent a terminally differentiated effector population which is destined for clearance by apoptosis at the end of the immune response.