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Science 302 (5647): 1041-1043

Copyright © 2003 by the American Association for the Advancement of Science

Control of Effector CD8+ T Cell Function by the Transcription Factor Eomesodermin

Erika L. Pearce,1 Alan C. Mullen,1 Gislâine A. Martins,1 Connie M. Krawczyk,1 Anne S. Hutchins,1 Valerie P. Zediak,1 Monica Banica,1 Catherine B. DiCioccio,1 Darrick A. Gross,1 Chai-an Mao,4 Hao Shen,2 Nezih Cereb,5 Soo Y. Yang,5 Tullia Lindsten,1 Janet Rossant,4 Christopher A. Hunter,3 Steven L. Reiner1*

Abstract: Activated CD8+ T cells play a critical role in host defense against viruses, intracellular microbes, and tumors. It is not clear if a key regulatory transcription factor unites the effector functions of CD8+ T cells. We now show that Eomesodermin (Eomes), a paralogue of T-bet, is induced in effector CD8+ T cells in vitro and in vivo. Ectopic expression of Eomes was sufficient to invoke attributes of effector CD8+ T cells, including interferon-{gamma} (IFN-{gamma}), perforin, and granzyme B. Loss-of-function analysis suggests Eomes may also be necessary for full effector differentiation of CD8+ T cells. We suggest that Eomesodermin is likely to complement the actions of T-bet and act as a key regulatory gene in the development 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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CXCR3 Deficiency Increases Susceptibility to Genital Herpes Simplex Virus Type 2 Infection: Uncoupling of CD8+ T-Cell Effector Function but Not Migration.
M. Thapa and D. J. J. Carr (2009)
J. Virol. 83, 9486-9501
   Abstract »    Full Text »    PDF »
CD4-CD8 Lineage Differentiation: Thpok-ing into the Nucleus.
L. Wang and R. Bosselut (2009)
J. Immunol. 183, 2903-2910
   Abstract »    Full Text »    PDF »
Gene Regulation and Chromatin Remodeling by IL-12 and Type I IFN in Programming for CD8 T Cell Effector Function and Memory.
P. Agarwal, A. Raghavan, S. L. Nandiwada, J. M. Curtsinger, P. R. Bohjanen, D. L. Mueller, and M. F. Mescher (2009)
J. Immunol. 183, 1695-1704
   Abstract »    Full Text »    PDF »
Type 17 CD8+ T cells display enhanced antitumor immunity.
C. S. Hinrichs, A. Kaiser, C. M. Paulos, L. Cassard, L. Sanchez-Perez, B. Heemskerk, C. Wrzesinski, Z. A. Borman, P. Muranski, and N. P. Restifo (2009)
Blood 114, 596-599
   Abstract »    Full Text »    PDF »
Histone Acetyltransferase CBP Is Vital To Demarcate Conventional and Innate CD8+ T-Cell Development.
T. Fukuyama, L. H. Kasper, F. Boussouar, T. Jeevan, J. van Deursen, and P. K. Brindle (2009)
Mol. Cell. Biol. 29, 3894-3904
   Abstract »    Full Text »    PDF »
IL-23 Promotes the Production of IL-17 by Antigen-Specific CD8 T Cells in the Absence of IL-12 and Type-I Interferons.
M. M. Curtis, S. S. Way, and C. B. Wilson (2009)
J. Immunol. 183, 381-387
   Abstract »    Full Text »    PDF »
T-bet-Deficient NOD Mice Are Protected from Diabetes Due to Defects in Both T Cell and Innate Immune System Function.
J. H. Esensten, M. R. Lee, L. H. Glimcher, and J. A. Bluestone (2009)
J. Immunol. 183, 75-82
   Abstract »    Full Text »    PDF »
Requirement for AHNAK1-mediated calcium signaling during T lymphocyte cytolysis.
D. Matza, A. Badou, M. K. Jha, T. Willinger, A. Antov, S. Sanjabi, K. S. Kobayashi, V. T. Marchesi, and R. A. Flavell (2009)
PNAS 106, 9785-9790
   Abstract »    Full Text »    PDF »
T-bet Inhibits the In Vivo Differentiation of Parasite-Specific CD4+ Th17 Cells in a T Cell-Intrinsic Manner.
S. Guo, D. Cobb, and R. B. Smeltz (2009)
J. Immunol. 182, 6179-6186
   Abstract »    Full Text »    PDF »
Many different V{beta} CDR3s can reveal the inherent MHC reactivity of germline-encoded TCR V regions.
K. Rubtsova, J. P. Scott-Browne, F. Crawford, S. Dai, P. Marrack, and J. W. Kappler (2009)
PNAS 106, 7951-7956
   Abstract »    Full Text »    PDF »
The molecular signature of CD8+ T cells undergoing deletional tolerance.
I. A. Parish, S. Rao, G. K. Smyth, T. Juelich, G. S. Denyer, G. M. Davey, A. Strasser, and W. R. Heath (2009)
Blood 113, 4575-4585
   Abstract »    Full Text »    PDF »
IL-23 Drives Pathogenic IL-17-Producing CD8+ T Cells.
B. Ciric, M. El-behi, R. Cabrera, G.-X. Zhang, and A. Rostami (2009)
J. Immunol. 182, 5296-5305
   Abstract »    Full Text »    PDF »
Impaired CD4 and CD8 Effector Function and Decreased Memory T Cell Populations in ICOS-Deficient Patients.
N. Takahashi, K. Matsumoto, H. Saito, T. Nanki, N. Miyasaka, T. Kobata, M. Azuma, S.-K. Lee, S. Mizutani, and T. Morio (2009)
J. Immunol. 182, 5515-5527
   Abstract »    Full Text »    PDF »
Notch Regulates Cytolytic Effector Function in CD8+ T Cells.
O. H. Cho, H. M. Shin, L. Miele, T. E. Golde, A. Fauq, L. M. Minter, and B. A. Osborne (2009)
J. Immunol. 182, 3380-3389
   Abstract »    Full Text »    PDF »
IL-21-Mediated Potentiation of Antitumor Cytolytic and Proinflammatory Responses of Human V{gamma}9V{delta}2 T Cells for Adoptive Immunotherapy.
A. Thedrez, C. Harly, A. Morice, S. Salot, M. Bonneville, and E. Scotet (2009)
J. Immunol. 182, 3423-3431
   Abstract »    Full Text »    PDF »
Eomesodermin Requires Transforming Growth Factor-{beta}/Activin Signaling and Binds Smad2 to Activate Mesodermal Genes.
P. Picozzi, F. Wang, K. Cronk, and K. Ryan (2009)
J. Biol. Chem. 284, 2397-2408
   Abstract »    Full Text »    PDF »
Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs.
F. Cruz-Guilloty, M. E. Pipkin, I. M. Djuretic, D. Levanon, J. Lotem, M. G. Lichtenheld, Y. Groner, and A. Rao (2009)
J. Exp. Med. 206, 51-59
   Abstract »    Full Text »    PDF »
The cytolytic enzymes granyzme A, granzyme B, and perforin: expression patterns, cell distribution, and their relationship to cell maturity and bright CD57 expression.
P. K. Chattopadhyay, M. R. Betts, D. A. Price, E. Gostick, H. Horton, M. Roederer, and S. C. De Rosa (2009)
J. Leukoc. Biol. 85, 88-97
   Abstract »    Full Text »    PDF »
T-bet and Eomesodermin Play Critical Roles in Directing T Cell Differentiation to Th1 versus Th17.
Y. Yang, J. Xu, Y. Niu, J. S. Bromberg, and Y. Ding (2008)
J. Immunol. 181, 8700-8710
   Abstract »    Full Text »    PDF »

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