Regulation of NKT cell development by SLAP2 (P1470)

Abstract

Abstract NKT cell function in animal models is highly variable. This variation is likely due to functionally distinct subpopulations of NKT cells that are present to different degrees in each mouse strain. NKT precursors proceed through several developmental stages marked by the sequential expression of activation markers and NK cell receptors. At each step of development, NKT precursors receive signals that promote progression to the next stage. The nature of these signals is not completely understood, however T cell receptor (TCR), SLAM receptor and cytokine signaling are important. Src-Like adaptor protein 2 (SLAP2) is an adaptor protein that has been implicated in regulation of TCR and cytokine signaling in cell lines. While TCR signaling and development of conventional αβ T cells are normal in SLAP2-/- thymocytes, NKT cell development is altered. SLAP2-deficient thymocytes are enriched for immature NKT cells, a population known to be biased towards IL-4 secretion. Consequently, a large increase in the proportion of IL-4-dependent "innate CD8 lymphocytes" is detected in the thymus of SLAP2-/- mice. We hypothesize that SLAP2 modulates currently undefined signaling pathways that are important for NKT cell development.