Regulation of γδ T cell effector programming by the SLAM/SAP signaling pathway 3806

Description Gamma delta (γδ) T cells are innate-like T cells that shape the developing adaptive immune response through their ability to rapidly produce large amounts of cytokines such as IL-17 (γδT17) and IFN-γ (γδT1). Unlike conventional αβ T cells, γδ T cells acquire their effector function during thymic development through mechanisms that remain unclear. Previously, we reported that the SLAM/SAP signaling pathway regulates both thymic γδT17 and γδT1 development. Here, we investigated whether the SLAM/SAP signaling pathway regulates thymic γδ T cell effector programming by modulating TCR signal strength. Using a B6.Nur77GFP.SAP-/- reporter strain, we compared the expression of canonical markers of TCR signaling, Nur77 transcription and CD5 protein expression, between B6 and B6.SAP-/- mice. Ex vivo analysis of embryonic day 17 thymic γδ T cells revealed both decreased CD5 expression and increased Nur77-GFP expression in B6.Nur77GFPSAP-/- γδ T cells. In vitro stimulation of B6.Nur77GFP and B6.Nur77GFPSAP-/- thymocytes with anti-TCRδ revealed increased GFP expression in B6.Nur77GFPSAP-/- γδ T cells. Similarly, anti-CD3 stimulation revealed increased Erk phosphorylation in B6.SAP-/- thymic γδ T cells. These data suggest that the SLAM/SAP signaling pathway can modulate TCR signal strength of thymic γδ T cells, but that it may utilize fundamentally different modes of action in cells destined for the γδT17 and γδT1 effector Topic Categories Hematopoiesis and Immune System Development (HEM)