IMMUNOBIOLOGY Enhanced development of CD4 T cells in the absence of Itk results in elevated IgE production

The Tec kinase Itk is critical for the devel-opment of T cells as well as differentia-tion of CD4 T cells into Th2 cells. Itk null mice have defects in the production of Th2 cytokines; however, they paradoxi-cally have significant elevations in serum IgE. Here we show that Itk null mice have increased numbers of T cells in the thymus and spleen. This includes el-evated numbers of CD4 T cell, the majority of which carry the V1.1 and V6.2/3 T-cell receptor with a distinct phenotype. The development of these CD4 T cells is T cell intrinsic, indepen-dent of either major histocompatibility complex class I or class II, and is favored during development in the absence of Itk. Itk null CD4 T cells secrete significant amounts of Th2 cytokines and can induce the secretion of IgE by wild-type B cells. Our data indicate that Itk plays important role in regulating T-cell development and function. In addition, our data indi-cate that the elevated IgE observed in Itk-deficient mice is due in part to the enhanced development of CD4 T cells in the absence of Itk. (Blood. 2009;114: 564-571