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 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. When stimulated through the γδ TCR, Itk -/- γδT cells produce high levels of Th2 cytokines, but diminished IFNγ. in addition, activated Itk -/- γδT 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 in ltk -/- mice, most notably the Vy1.1 +V86.3 + subset that represents the dominant population of γδ NKT cells, Iltk -/- 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.
|Original language||English (US)|
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - May 19 2009|
- T cell development
- T cell differentiation
- T cell signaling