The Tec kinases Itk and Rlk regulate NKT cell maturation, cytokine production, and survival
Biochemistry & Molecular Pharmacology
Graduate School of Biomedical Sciences; Department of Pathology
Life Sciences | Medicine and Health Sciences
The Tec kinases Itk and Rlk are required for efficient positive selection of conventional CD4+ and CD8+ T cells in the thymus. In contrast, recent studies have shown that these Tec kinases are dispensable for the development of CD8+ T cells with characteristics of innate T cells. These findings raise questions about the potential role of Itk and Rlk in NKT cell development, because NKT cells represent a subset of innate T cells. To address this issue, we examined invariant NKT cells in Itk-/- and Itk/Rlk-/- mice. We find, as has been reported previously, that Itk-/- mice have reduced numbers of NKT cells with a predominantly immature phenotype. We further show that this defect is greatly exacerbated in the absence of both Itk and Rlk, leading to a 7-fold reduction in invariant NKT cell numbers in the thymus of Itk/Rlk-/- mice and a more severe block in NKT cell maturation. Splenic Itk-/- and Itk/Rlk-/- NKT cells are also functionally defective, because they produce little to no cytokine following in vivo activation. Tec kinase-deficient NKT cells also show enhanced cell death in the spleen. These defects correlate with greatly diminished expression of CD122, the IL-2R/IL-15R beta-chain, and impaired expression of the T-box transcription factor, T-bet. These data indicate that the Tec kinases Itk and Rlk provide important signals for terminal maturation, efficient cytokine production, and peripheral survival of NKT cells.
DOI of Published Version
J Immunol. 2008 Mar 1;180(5):3007-18.
Journal of immunology (Baltimore, Md. : 1950)
Felices M, Berg LJ. (2008). The Tec kinases Itk and Rlk regulate NKT cell maturation, cytokine production, and survival. GSBS Student Publications. https://doi.org/10.4049/jimmunol.180.5.3007. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1457