Protein Kinase C η Is Required for T Cell Activation and Homeostatic Proliferation

Protein kinase C eta (PKC eta) is abundant in T cells and is recruited to the immunological synapse that is formed between a T cell and an antigen-presenting cell; however, its function in T cells is unknown. We showed that PKC eta was required for the activation of mature CD8(+) T cells through the T cell receptor. Compared with wild-type T cells, PKC eta T-/- cells showed poor proliferation in response to antigen stimulation, a trait shared with T cells deficient in PKC theta, which is the most abundant PKC isoform in T cells and was thought to be the only PKC isoform with a specific role in T cell activation. In contrast, only PKC eta-deficient T cells showed defective homeostatic proliferation, which requires self-antigen recognition. PKC eta was dispensable for thymocyte development; however, thymocytes from mice doubly deficient in PKC eta and PKC theta exhibited poor development, indicating some redundancy between the PKC isoforms. Deficiency in PKC eta or PKC theta had opposing effects on the relative numbers of CD4(+) and CD8(+) T cells. PKC eta(-/-) mice had a higher ratio of CD4(+) to CD8(+) T cells compared to that of wild-type mice, whereas PKC eta(-/-) mice had a lower ratio. Mice deficient in both isoforms exhibited normal cell ratios. Together, these data suggest that PKC eta shares some redundant roles with PKC theta in T cell biology and also performs nonredundant functions that are required for T cell homeostasis and activation.