T cell-intrinsic protein kinase D3 is dispensable for the cells' activation.

Abstract

Protein kinases D (PKDs) are implicated in T cell receptor (TCR) signaling. Of the two Tcell-expressed isoforms PKD2 and PKD3, however, only the former one is rather well understood in this immune cell type. Recently, we have observed a putative hyper-phenotype of T cells from conventional PKD3-knockout mice, which we explained as a secondary effect due to a skewed T cell compartment from naïve towards effector/memory Tcells already under steady state conditions. Nonetheless, to this end it is not clear whether these aberrations are mediated by a Tcell-intrinsic or -extrinsic function of PKD3. To address this question, we have investigated mice lacking PKD3 specifically in the Tcell compartment. We could show that Tcells from CD4-Cre-driven conditional knockout mice did not phenocopy the ones from conventional PKD3-knockout mice. In brief, no skewing in the Tcell compartment of peripheral lymphoid organs, no hyper-activation upon stimulation in vitro or in vivo as well as no aberrations in follicular helper T cells (TFH) upon immunization were observed. Hence, although PKD3 is strongly regulated upon TCR stimulation, in Tcells this kinase seems to be dispensable for their activation. The described skewing in the Tcell compartment of conventional PKD3-deficient mice seems to be mediated by Tcell-extrinsic mechanisms, thus once more emphasizing the importance of cell type-specific mouse models.