Development of PLZF-expressing γδ NKT cells in Itk-/- mice (115.13)

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. We have previously shown the cause of this phenotype is due to the increase of the mature Vγ1.1+Vδ6.3+ (V6) subset of γδ T cells in Itk-/- mice. Wild type V6 γδ T cells display characteristics similar to αβ NKT cells including dual secretion of IL-4 and IFNγ along with expression of the transcription factor PLZF; therefore they are γδ NKT cells. Along with increased proportions of mature V6 cells in Itk-/- mice, V6 cells in Itk-/- mice have increased IL-4 secretion and elevated levels of PLZF expression. Based upon PLZF expression and the use of the IL-4 reporter (4Get) mice, our data indicate that γδ NKT cells have similar differentiation stages as αβ NKT cells, and that Itk-/- γδ NKT cells are blocked during development. 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.