Tec kinase Itk in γδT cells is pivotal for controlling IgE production in vivo

Publisher Website
Google Scholar
Abstract
In conventional αβ T cells, the Tec family tyrosine kinase Itk is required for signaling downstream of the T cell receptor (TCR). Itk also regulates αβ T cell development, lineage commitment, and effector function. A well established feature ofItk−/−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 inItk−/−Tcrd−/−mice. When stimulated through the γδ TCR, Itk−/−γδ T cells produce high levels of Th2 cytokines, but diminished IFNγ. In addition, activated Itk−/−γδ T cells up-regulate costimulatory molecules important for B cell help, suggesting that they may directly promote B cell activation and Ig class switching. Furthermore, we find that γδ T cells numbers are increased inItk−/−mice, most notably the Vγ1.1+Vδ6.3+subset that represents the dominant population of γδ NKT cells.Itk−/−γδ NKT cells also have increased expression of PLZF, a transcription factor required for αβ NKT cells, indicating a common molecular program between αβ and γδ NKT cell lineages. 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.