| First Author | Felices M | Year | 2008 |
| Journal | J Immunol | Volume | 180 |
| Issue | 5 | Pages | 3007-18 |
| PubMed ID | 18292523 | Mgi Jnum | J:131540 |
| Mgi Id | MGI:3773943 | Doi | 10.4049/jimmunol.180.5.3007 |
| Citation | Felices M, et al. (2008) The tec kinases itk and rlk regulate NKT cell maturation, cytokine production, and survival. J Immunol 180(5):3007-18 |
| abstractText | 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. |
