The Wiskott-Aldrich Syndrome protein (WASp) controls iNKT cell effector function. (50.39)

Abstract

Abstract The Wiskott-Aldrich Syndrome protein (WASp) is a regulator of actin remodeling in hematopoietic cells. In T cells, WASp is required for a long-lived Immunological Synapse (IS) and TCR-mediated cytokine production. We recently published that WASp is fundamental in the biology of iNKT cells, a peculiar T cell subset activated by glycosphingolipid antigens presented by APC. We showed that murine was-/- iNKT cells were defective in IL-4 and IFN-γ production upon in vivo activation. It remains an open issue whether this functional impairment is caused by a cell autonomous functional defect of was-/- iNKT cells or by an impaired crosstalk between iNKT cells and APC. To address this issue we analyzed cytokine production upon in vitro activation of wt and was-/- iNKT cells by wt and was-/- DC. The data obtained indicate the defective IL-4 production due to a was-/- iNKT cell autonomous defect and the lower IFN-γ production caused by an inefficient crosstalk between was-/- iNKT cells and was-/- DC. However was-/- iNKT cells produced sustained levels of cytokines upon in vitro stimulation with TPA and Ionomycin, suggesting a TCR-mediated functional impairment of these cells. Supporting this hypothesis was-/- iNKT cells presented a decreased TCR avidity. Altogether these results demonstrate the relevance of WASp in TCR-mediated effector function of iNKT cells. Ongoing studies are aimed at evaluating the ability to properly form the IS by was-/- iNKT cell and APC.