ERK2 has an important role for CD4⁺T cell survival and function

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 member of the mitogen activated protein kinase (MAPK) family which, in T cells, transduces crucial signals such as TCR engagement, CD28 co-stimulation, and cytokine signaling. Upon activation, these signals are carefully coordinated to initiate specific gene expression programs to direct the expansion and differentiation of Ag-specific T cells. Precise control of these signaling mechanisms is needed to maintain homeostasis; dysregulation can result in inappropriate immune responses. In this study we determined the role of ERK2 for the effector function of peripheral CD4+ T cells using a model wherein T cell-specific deletion of ERK2 (ERK2Δ) could be monitored in vivo via eYFP expression. The results showed that ERK2 Δ CD4+ T cells emigrated from the thymus and represented a large part of the peripheral T cell pool. Of note, increased numbers of peripheral ERK2Δ CD4+ T cells expressed activation markers (CD25, CD44, and CD69), proliferated upon IL-2, IL-7, and IL-15 cytokine stimulation, and expanded in vivo; however ERK2Δ CD4+ T cells had substantially impaired survival in vitro. Importantly, the functional analysis of ERK2Δ CD4+ T cells showed that ERK2 is important to protect Ag-specific CD4+ T cells from the pro-apoptotic signaling elicited by secondary antigen encounter.