The kinase activity of ITK is not required for iNKT cell development and function

Abstract

Invariant natural killer T (iNKT) cells are a unique subset of innate T lymphocytes that are selected by CD1d. They have diverse immune regulatory functions via the rapid production of interferon‐gamma (IFN‐gamma) and interleukin‐4 (IL‐4). In the absence of ITK, a Tec family non‐receptor tyrosine kinase, mice exhibit a significant defect in iNKT cell development, and residual iNKT cells have defective cytokine secretion. Although the kinase activity is important for ITK, several studies have shown that ITK can activate pathways that are independent of its kinase activity. Whether the requirement for ITK in iNKT cells development and function is dependent on its kinase activity is not clear. We report here that the kinase activity of ITK is not fully required for the mature and activation of iNKT cells. In mice which carry a kinase‐domain deleted ITK in the ITK null background (ItkΔKinTg/Itk−/ −), we observe significant rescue of mature iNKT cells in the thymus and spleen compared with ITK null mice. Furthermore, unlike ITK−/ − iNKT cells, iNKT cells from ItkΔKinTg/Itk−/ − mice were able to secrete IFN‐gamma and IL‐4 upon exposure to α‐GalCer. These data indicate that ITK uses a scaffolding function in the signaling pathway leading to the maturation and activation of iNKT cells.