Protein kinase Cepsilon is dispensable for TCR/CD3-signaling.

PKCepsilon has been strongly linked to cell activation and proliferation in many cell types, including leukemic T-cell lines. In particularly, an essential role of PKCepsilon has been established in the IKK-beta/I-kappaB/NF-kappaB transactivation cascade. To study the physiological function of PKCepsilon in primary T-cells, we used our newly established PKCepsilon null mice. Unexpectedly, however, we did not reveal any defect in the development and function of CD3+ T-cells. Proliferative responses as well as IL-2 cytokine secretion of PKCepsilon-deficient T-cells induced by allogenic MHC, plate-bound anti-CD3 antibodies (with or without anti-CD28 costimulation), or mitogenic stimuli such as phorbol ester and Ca2+ ionophore were comparable with wild-type controls. Consistently, after CD3/CD28 engagement, deficiency of PKCepsilon did not impair NF-kappaB transactivation as well as CD25, CD44 and CD69 induction. Thus, PKCepsilon-deficient T-cells had similar physiological thresholds for activation in vitro. This finding suggests that PKCepsilon plays a redundant role in TCR-induced regulation of T-cell proliferation.