The Tec family tyrosine kinases, Itk and Rlk, are expressed in thymocytes and peripheral T cells and regulate thresholds of T cell receptor signaling. Yet little is known about the specific role of Itk- and Rlk-dependent signals in CD8+ T cell maturation. We show here that Itk-/- and Rlk-/-Itk-/- mice were nearly devoid of conventional CD8+ T cells and, instead, contained a large population of CD8+ T cells that bear striking similarity to lineages of innate lymphocytes. Itk-/- and Rlk-/-Itk-/- CD8+ thymocytes and T cells were CD44hi, CD122+, and NK1.1+; were able to produce interferon-γ directly ex vivo; and were dependent on interleukin-15. Itk-/- and Rlk-/-Itk-/- CD8+ thymocytes expressed abundant transcripts for the T box transcription factor, eomesodermin, correlating with their phenotype and function. These data indicate a critical role for Itk and Rlk in conventional CD8+ T cell development in the thymus.
Bibliographical noteFunding Information:
We thank Dr. Pamela Schwartzberg, Dr. Chyung-Ru Wang, Dr. Joonsoo Kang, Dr. B.J. Fowlkes, and Dr. Shane Mayack for helpful discussions and insightful comments. We thank Regina Whitehead, Dr. Joe Maciaszek, Dr. Michael Brehm, and Dr. Sung-Kwon Kim for technical assistance. This work was supported by NIH grants AI37584 (L.J.B.) and AI0161699 (S.L.R.) and by a grant from the Center for Disease Control, CI00101 (L.J.B.).