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CUTTING EDGE |
* Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104; and
The Wistar Institute, Philadelphia, PA 19104
Cytokines are critical determinants for specification of lineage-defining transcription factors of CD4+ T cell subsets. Little is known, however, about how cytokines regulate expression of T-bet and eomesodermin (Eomes) in effector and memory CD8+ T cells. We now report that IL-12, a signature of cell-mediated immunity, represses Eomes while positively regulating T-bet in effector CD8+ T cells during infection with Listeria monocytogenes. After resolution of infection and abatement of IL-12 signaling, Eomes expression rises whereas T-bet expression declines in memory CD8+ T cells. Eomes becomes derepressed in effector cells by ablation of IL-12 signaling. In the absence of IL-12, the dynamics of clonal expansion and contraction are also perturbed. Together, these results reveal how a pathogen-associated signal, such as IL-12, could act as a switch, regulating appropriate clonal growth and decline while, in parallel, shaping a unique pattern of fate-determining transcription factors.
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 This work was supported by National Institutes of Health Grants AI061699 and AI42370 (to S.L.R.) and AI071309-01 (to E.J.W.), the Commonwealth Universal Research Enhancement Program, Pennsylvania Department of Health (to E.J.W.), and the Abramson Family.
2 Address correspondence and reprint requests to Dr. Steven L. Reiner, Abramson Family Cancer Research Institute, University of Pennsylvania, BRB II/III, Rm. 414, 421 Curie Blvd., Philadelphia, PA 19104. E-mail address: sreiner{at}mail.med.upenn.edu
3 Abbreviations used in this paper: LCMV, lymphocytic choriomeningitis virus; ChIP, chromatin immunoprecipitation; CNS, conserved non-coding sequence; LMgp33, rListeria monocytogenes expressing GP33–41.
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