CD4+ T cell regulation of CD25 expression controls the development of effector CD8+ T cells in acute and chronic virus infections. (137.14)

Abstract

Abstract Both CD4+ T cell help and IL-2 have been postulated to ‘program’ activated CD8+ T cells for memory cell development. However, the link between these two signals has not been well elucidated. We have studied effector and memory CD8+ T cell differentiation following infection with vaccinia virus and murine gammaherpes virus in the absence of both CD4+ T cells and CD25. Expression of CD25 on antigen-specific CD8+ T cells peaked 3-4 days after infection and was dependent on CD4+ T cell help. CD4+ T cell or CD25-deficiency led to normal early effector CD8+ T cell differentiation, but a subsequent lack of accumulation of CD8+ T cells resulting in overall decreased memory cell generation. Interestingly, KLRG1high CD127low short-lived effector cells were diminished in the absence of IL-2 signaling, while memory precursors remained intact. Interestingly, the mononucleosis-like expansion of Vβ4+ T cells seen in mice infected with MHV-68 was impaired in a similar fashion to antigen specific responses. Upon secondary antigen encounter, CD25-deficient CD8+ T cells were capable of undergoing robust expansion, but short-lived effector development was again impaired. These results demonstrate that CD4+ help and IL-2 signaling are linked via CD25 upregulation, which controls the expansion and differentiation of antigen-specific effector CD8+ T cells.