The Erk2 MAPK Regulates CD8 T Cell Proliferation and

The magnitude of T cell responses is determined by proliferation and survival decisions made by the responding cells. We now demonstrate that the Erk MAPK pathway plays a critical role in these cell fate decisions within CD8 T cells. While Erk1 is dispensable for all aspects of CD8 T cell activation, Erk2 is required for the proliferation of CD8 T cells activated in the absence of costimulation. Surprisingly, Erk2 is not required for proliferation following the addition of a costimulatory signal in vitro, or upon viral infection in vivo, but regulates the size of the responding population by enhancing cell survival. An important com-ponent of this Erk2-derived signal is the transcriptional regulation of Bcl-2 family members Bcl-xL and Bim, and impaired Erk2-deficient CD8 T cell survival can be rescued by genetic ablation of Bim. These studies ascribe multifaceted functions specific to Erk2 in CD8 T cell activation, proliferation, and survival. The Journal of Immunology, 2008, 181: 7617–7629. N aive T cells are activated via TCR-mediated recognitionof antigenic peptides complexed to the appropriate MHCmolecules. Upon activation, these cells proliferate rap-idly and can undergo up to a 105-fold expansion within a period of a week to generate an impressive number of effector T cells (1–3). In addition to proliferation, survival vs death decisions that are made by responding Ag-specific T cells during this expansion phase are critical in determining the outcome of the T cell re-sponse. These diverse cell fate choices are the result of a summa