CD4+ and CD8+ T Cell Survival Is Regulated Differentially by Protein Kinase Cθ, c-Rel, and Protein Kinase B

Abstract

An effective immune response requires the expansion and survival of a large number of activated T cells. This study compared the role of protein kinase C (PKC)θ and associated signaling molecules in the survival of activated primary CD4+ vs CD8+ murine T cells. We demonstrate that the absence of PKCθ resulted in a moderate survival defect in CD4+ T cells and a striking survival defect of CD8+ T lymphocytes. CD8+ T cells lacking the c-Rel, but not the NF-κB1/p50, member of the NF-κB family of transcription factors displayed a similar impairment in cell survival as PKCθ−/− CD8+ T lymphocytes. This implicates c-Rel as a key target of PKCθ-mediated survival signals in CD8+ T cells. In addition, both c-Rel−/− and PKCθ−/− T cells also displayed impaired expression of the antiapoptotic Bcl-xL protein upon activation. Changes in Bcl-xL expression, however, did not correlate with the survival of CD4+ or CD8+ lymphocytes. The addition of protein kinase B-mediated survival signals could restore partially CD4+ T cell viability, but did not dramatically influence CD8+ survival. Active protein kinase B was also unable to restore proliferative responses in CD8+ PKCθ−/− T cells. The survival of CD4+ and CD8+ T cells deficient in either PKCθ or c-Rel, however, was promoted by the addition of IL-2. Collectively, these data demonstrate that CD4+ and CD8+ T cell survival signals are differentially programmed.