NKAP is required for iNKT cell development (P4450)

Abstract Invariant Natural Killer T cells (iNKT) are innate lineage of lymphocytes with distinct developmental pathway than conventional αβ T cells. The transcriptional repressor NKAP is required for early T cell development and maturation of conventional αβ T cells. Using CD4-cre NKAP cKO mice, we show that NKAP is required for positive selection of thymocytes into the iNKT cells lineage. Deletion of NKAP using CD4-cre leads to an early block in iNKT cell development at the DP stage. This cell intrinsic defect was not due to decreased DP thymocyte survival or inability of NKAP deficient thymocytes to rearrange their Vα14-Jα18 TCR. Moreover, ectopic over-expression of Vα14-Jα18 invariant TCR α chain rescued the development of iNKT cells. This suggests that NKAP plays a role in the positive selection of thymocytes into the iNKT cell lineage. Interestingly, conditional deletion of NKAP associated protein Hdac3 using CD4-cre also leads to a similar block in iNKT cell development, but not conventional T cell development. This is first evidence demonstrating for an Hdac in T cell development. Whether NKAP and Hdac3 work together functionally to regulate the positive selection of DP thymocytes into iNKT cell lineage is currently being investigated.