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Control of Effector CD8+ T Cell Function by the Transcription Factor Eomesodermin
Erika L. Pearce,1Alan C. Mullen,1Gislâine A. Martins,1Connie M. Krawczyk,1Anne S. Hutchins,1Valerie P. Zediak,1Monica Banica,1Catherine B. DiCioccio,1Darrick A. Gross,1Chai-an Mao,4Hao Shen,2Nezih Cereb,5Soo Y. Yang,5Tullia Lindsten,1Janet Rossant,4Christopher A. Hunter,3Steven L. Reiner1*
Activated CD8+ T cells play a critical role in host defenseagainst viruses, intracellular microbes, and tumors. It is notclear if a key regulatory transcription factor unites the effectorfunctions of CD8+ T cells. We now show that Eomesodermin (Eomes),a paralogue of T-bet, is induced in effector CD8+ T cells invitro and in vivo. Ectopic expression of Eomes was sufficientto invoke attributes of effector CD8+ T cells, including interferon-(IFN-), perforin, and granzyme B. Loss-of-function analysissuggests Eomes may also be necessary for full effector differentiationof CD8+ T cells. We suggest that Eomesodermin is likely to complementthe actions of T-bet and act as a key regulatory gene in thedevelopment of cell-mediated immunity.
1 Abramson Family Cancer Research Institute, and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. 2 Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA. 3 Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA. 4 Samuel Lunenfeld Research Institute, and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada M5G 1X5. 5 Histogenetics, and Center for Genetic Polymorphism, Ossining, NY 10562, USA.
* To whom correspondence should be addressed. E-mail: sreiner{at}mail.med.upenn.edu
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