Expanded γδ T cell populations in absence of transcription factor PU.1 (36.49)

Abstract

Abstract T cell development is characterized by a succession of developmental stages that lead to the generation of mature αβ and γδ T cells. γδ T cells are considered innate cells that critically contribute to host defense. PU.1, an Ets family transcription factor, also identified as the spleen focus forming virus proviral integration site-1 (Sfpi-1) is essential for early stages of T cell development and is down regulated during the pro T-cell stage. PU.1 is expressed in Th2 cells but not Th1 cells. Expression of PU.1 in other T cell subsets has not been studied extensively. In this study, we show that PU.1 is expressed in γδ T cells, and in mice that specifically lack PU.1 in T cells using an lck-Cre transgene with a conditional Sfpi1 allele (Sfpilck-/-) there are increased numbers of γδ T cells in spleen, thymus and in the intestine when compared to wild type mice. The increase in γδ T cell numbers in PU.1 deficient mice is reflected in several subsets examined (Vγ2T, Vγ3T and Vδ4T). In mice where PU.1 was deleted using a CD4-Cre transgene, the expansion of γδ T cell numbers was restricted to the intestinal population. PU.1-deficient γδ T cells secrete higher levels of IL-17 than wild type cells, but similar levels of IFN-γ. Thus, our data show that PU.1 is expressed in γδ T cells and that deletion of PU.1 results in γδ T cell expansion. This suggests that PU.1 has a negative influence on γδ T cell development or expansion.