Partial rescue of Itk-/- iNKT cell development by Txk/Rlk reveals a unique role for Itk in the survival of iNKT cells. (50.40)

Abstract

Abstract Invariant natural killer T (iNKT) cells are a distinct population of innate T lymphocytes that play important role in the immune response. Itk and Txk/Rlk are Tec family kinases that are expressed in iNKT cells, with the expression level of Itk about 7-fold higher than that of Txk. It has been reported that the Itk null mice have reduced iNKT cell frequency and numbers, as well as defects in iNKT cell development and cytokine secretion, all of which are exacerbated in the Itk/Txk DKO mice. By contrast, the phenotype of iNKT cells in Txk null mice is similar to that from WT mice. In order to determine whether Itk and Txk plays distinct roles in iNKT cell development and function, we examined the iNKT cells in Tg(Lck-Txk)/Itk-/- mice, which over express Txk in T cells to the similar level as Itk. Over expression of Txk rescues the maturation and cytokine secretion of iNKT cells in Itk null mice. It also rescues the altered expression of transcription factor T-bet, eomesodermin and PLZF. By contrast, over expression of Txk does not rescue the reduced iNKT cell numbers in Itk null mice, which is due to the failure to rescue the increased apoptosis observed in Itk-/- iNKT cells. These data suggest that Txk plays an overlapping role with Itk in iNKT cell development and function, but that Itk also has a unique function in the survival of iNKT cells.