PKCtheta and Itk functionally interact during primary mouse CD3+ T cell activation

PKCtheta serine/threonine and Itk tyrosine protein kinases have been implicated in T lymphocyte signal transmission. We observed a PKCtheta/Itk complex after T cell activation, raising the possibility that PKCtheta and Itk might interact functionally during T cell development and response. To address this question PKCtheta/Itk double knockout mice were generated and T cell activation responses were compared to single deficiencies as well as to wild type controls. Consistent with previous reports, Itk and PKCtheta are required in modulating CD3(+) T cell cytokine secretion responses ex vivo. Itk- and PKCtheta-deficient cells show impaired NFAT/AP-1 and NF-kappaB transactivation responses, however the combined loss, did not exceed but partially rescue the strong NFAT and NF-kappaB activation defects observed in Itk(-/-) single-deficient T cells. Taken together, this provides evidence for a more complex functional crosstalk between Itk and PKCtheta during T cell receptor signalling then previously anticipated.