The Tec kinase Itk regulates conventional versus non-conventional CD8 T cell development (87.14)

Abstract

Abstract Mutations affecting the Tec kinases Itk and Rlk impair both positive and negative selection and alter CD4 and CD8 T cell development. We previously demonstrated that mature CD8 SP thymocytes and peripheral CD8 T cells in Itk−/− and Rlk−/−Itk−/− mice do not resemble conventional CD8 T cells. Instead, these cells express memory markers and can be selected on MHC class I expressed on hematopoietic cells, suggesting these cells resemble non-conventional MHC class Ib-selected “innate-type” cells. Indeed, Itk-deficiency increases positive selection on MHC class Ib in the Kb−/−Db−/− background. We further find that either improving TCR signaling with stronger signals orblocking CD28 costimulation, partially corrects memory phenotypes of Itk−/− CD8 T cells, arguing that different strength or quality of signals may lead to development of this distinct CD8 T cell population. Our results suggest that Tec kinases differentially regulate development of conventional versus non-conventional lymphocytes. The requirement for signals from hematopoietic cells for selection of these “innate-type” CD8 T cells in Itk−/− mice will be discussed.