The role of tec kinases in CD8+ T cell memory differentiation

The Tec family of non‐receptor tyrosine kinases are involved in the signaling pathways for a variety of hematopoietic cells. In T cells, three family members are expressed: Itk, Rlk, and Tec. Previously, we have determined that Itk and Rlk regulate the development of conventional CD8+ T cells. In the absence of Itk and Rlk, CD8 single positive (SP) CD44‐hi T cells develop in the thymus. These thymocytes rapidly secrete IFNγ upon stimulation, are dependent upon IL‐15 for survival, and express high levels of the T‐box transcription factor, eomesodermin . Thus, in the absence of Itk and Rlk, non‐conventional CD8+ T cells resembling innate lymphocytes develop. However, despite these developmental defects, Itk/Rlk and Itk deficient mice are able to clear LCMV. During a primary LCMV infection, we find defects in proliferation and TNFα secretion of virus‐specific CD8+ T cells. These defects are also seen during secondary challenge, in an adoptive transfer model, in addition to inefficient memory protection. We conclude that CD8+ T cell memory differentiation is defective in the absence of Itk/Rlk and Itk, and that the innate lymphocytes formed in the absence of Itk/Rlk and Itk may impair memory differentiation after LCMV infection.