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The Erk2 MAPK Regulates CD8 T Cell Proliferation and Survival¹

Molecular Biology Section, Division of Biological Science, and the Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093

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 component of this Erk2-derived signal is the transcriptional regulation of Bcl-2 family members Bcl-x_L 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 costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ These studies were supported by a fellowship from the Leukemia and Lymphoma society (to W.N.D.) and National Institutes of Health Grant 5R01 AI021372-25 (to S.M.H.).

² Current address: Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320.

³ Address correspondence and reprint requests to Dr. Stephen M. Hedrick, Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0377. E-mail address: shedrick{at}ucsd.edu

⁴ Abbreviations used in this paper: WT, wild type; LCMV, lymphocytic choriomeningitis virus; PI, propidium iodide; VSV, vesicular stomatitis virus; VSV-OVA, VSV-expressing OVA.