Erk2-deficiency impairs the effector function of mature CD4+ T cells (IRM15P.455)

Abstract

Abstract Extracellular signal-regulated kinase 2 (Erk2) is required for CD4+T cell development and positive selection in the thymus, however the role of Erk2 in mature CD4+T cells is unknown. Erk2 is a key player of the mitogen activated protein kinase (MAPK) pathway which, in T cells, transduces crucial signals such as TCR engagement, CD28 co-stimulation, and cytokine binding. Upon activation, these signals are carefully coordinated to initiate gene expression programs, thus directing the expansion and differentiation of Ag-specific cells. The exquisite control of these signaling mechanisms is needed to maintain tolerance; dysregulation can result in inappropriate immune responses. In this study we used a mouse model with T cell-specific deletion of Erk2 to determine the role of Erk2 for CD4+T cell function. Our results show that increased numbers of Erk2∆CD4+T cells from naïve mice express markers for activation (CD25, CD44, and CD69). Further, Erk2∆CD4+T cells are able to survive and expand in vivo and proliferate upon IL-2, IL-7, and IL-15 cytokine stimulation. Importantly however, although the frequency and magnitude of Ag-specific Erk2∆CD4+T cell responses was comparable with controls upon antigen recall, secretion of IFN-g and IL-17 was significantly impaired. As CD4+T cells orchestrate immune responses primarily via cytokine production, our results suggest that Erk2 is required for CD4+T cell effector function.