Role of Itk in γδ T cell development and function (84.22)

Abstract

Abstract In conventional αβ T cells, the Tec family tyrosine kinase Itk is required for signaling downstream of the TCR. Itk also regulates αβ T cell development, lineage commitment, and effector function. A well established feature of Itk-/- mice is their inability to generate T helper type 2 (Th2) responses that produce IL-4, IL-5, and IL-13; yet these mice have spontaneously elevated levels of serum IgE and increased numbers of germinal center B cells. Here we show that the source of this phenotype is γδ T cells, as normal IgE levels are observed in Itk-/-Tcrd-/- mice. Further, we find that γδ T cells numbers are increased in Itk-/- mice, along with elevated proportions of γδ T cells expressing CD4 and NK1.1. When stimulated through the γδ TCR, Itk-/- γδ T cells produce high levels of the Th2 cytokines, but diminished IFNg. In addition, activated Itk-/- γδ T cells upregulate costimulatory molecules important for B cell help, suggesting that they may directly promote B cell activation and Ig class switching. Together, these data indicate that Itk signaling regulates γδ T cell lineage development and effector function, and is required to control IgE production in vivo.