Inositol 1,4,5-trisphosphate 3-kinase B (Itpkb) Controls Survival, Proliferation and Cytokine Production in Mouse Peripheral T Cells

Mice genetically-deficient for the B isoform of the inositol 1,4,5-trisphosphate 3-kinase (or Itpkb) have a severe defect in thymocytes differentiation and thus lack peripheral T cells. In order to study the functional role of Itpkb in peripheral T cells, we constructed a new mouse where a transgene encoding mouse Itpkb is specifically and transiently expressed in thymocytes of Itpkb(-)(/)(-) mice. This allows a partial rescue of mature thymocyte/T cell differentiation and thus the functional characterization of peripheral T cells lacking Itpkb. We show here that Itpkb(-)(/)(-) CD4(+) and CD8(+) peripheral T cells present important functional alterations. Indeed, an increased activated/memory phenotype as well as a decreased proliferative capacity and survival were detected in these T cells. These Itpkb-deficient peripheral T cells have also an increased capacity to secrete cytokines upon stimulation. Together, our present results define the important role of Itpkb in peripheral mature T cell fate and function in mouse, suggesting a potential role for Itpkb in autoimmunity.