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

Science, 7 November 2003
Vol. 302, Issue 5647, p. 1041-1043
DOI: 10.1126/science.1090148

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

  1. Erika L. Pearce1,
  2. Alan C. Mullen1,
  3. Gislâine A. Martins1,
  4. Connie M. Krawczyk1,
  5. Anne S. Hutchins1,
  6. Valerie P. Zediak1,
  7. Monica Banica1,
  8. Catherine B. DiCioccio1,
  9. Darrick A. Gross1,
  10. Chai-an Mao4,
  11. Hao Shen2,
  12. Nezih Cereb5,
  13. Soo Y. Yang5,
  14. Tullia Lindsten1,
  15. Janet Rossant4,
  16. Christopher A. Hunter3,
  17. Steven L. Reiner1,*
  1. 1 Abramson Family Cancer Research Institute, and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  2. 2 Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
  3. 3 Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
  4. 4 Samuel Lunenfeld Research Institute, and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada M5G 1X5.
  5. 5 Histogenetics, and Center for Genetic Polymorphism, Ossining, NY 10562, USA.
  1. * To whom correspondence should be addressed. E-mail: sreiner{at}mail.med.upenn.edu

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-γ (IFN-γ), 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.

  • Received for publication 6 August 2003.
  • Accepted for publication 10 September 2003.

Citation:

E. L. Pearce, A. C. Mullen, G. A. Martins, C. M. Krawczyk, A. S. Hutchins, V. P. Zediak, M. Banica, C. B. DiCioccio, D. A. Gross, C.-a. Mao, H. Shen, N. Cereb, S. Y. Yang, T. Lindsten, J. Rossant, C. A. Hunter, and S. L. Reiner, Control of Effector CD8+ T Cell Function by the Transcription Factor Eomesodermin. Science 302, 1041-1043 (2003).

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Cutting Edge: The Transcription Factor Eomesodermin Enables CD8+ T Cells To Compete for the Memory Cell Niche
A. Banerjee, S. M. Gordon, A. M. Intlekofer, M. A. Paley, E. C. Mooney, T. Lindsten, E. J. Wherry, and S. L. Reiner
J. Immunol. 185, 4988-4992 (1 November 2010)

T-bet and Eomesodermin Are Required for T Cell-Mediated Antitumor Immune Responses
Y. Zhu, S. Ju, E. Chen, S. Dai, C. Li, P. Morel, L. Liu, X. Zhang, and B. Lu
J. Immunol. 185, 3174-3183 (15 September 2010)

Defective feedback regulation of NF-{kappa}B underlies Sjogren's syndrome in mice with mutated {kappa}B enhancers of the I{kappa}B{alpha} promoter
B. Peng, J. Ling, A. J. Lee, Z. Wang, Z. Chang, W. Jin, Y. Kang, R. Zhang, D. Shim, H. Wang et al.
Proc. Natl. Acad. Sci. USA 107, 15193-15198 (24 August 2010)

Tc17 Cells Are Capable of Mediating Immunity to Vaccinia Virus by Acquisition of a Cytotoxic Phenotype
N. Yeh, N. L. Glosson, N. Wang, L. Guindon, C. McKinley, H. Hamada, Q. Li, R. W. Dutton, P. Shrikant, B. Zhou et al.
J. Immunol. 185, 2089-2098 (15 August 2010)

Antigen-specific clonal expansion and cytolytic effector function of CD8+ T lymphocytes depend on the transcription factor Bcl11b
S. Zhang, M. Rozell, R. K. Verma, D. I. Albu, D. Califano, J. VanValkenburgh, A. Merchant, J. Rangel-Moreno, T. D. Randall, N. A. Jenkins et al.
JEM 207, 1687-1699 (2 August 2010)

IFN-{alpha}{beta} and Self-MHC Divert CD8 T Cells into a Distinct Differentiation Pathway Characterized by Rapid Acquisition of Effector Functions
H. D. Marshall, A. L. Prince, L. J. Berg, and R. M. Welsh
J. Immunol. 185, 1419-1428 (1 August 2010)

Distal Regions of the Human IFNG Locus Direct Cell Type-Specific Expression
P. L. Collins, S. Chang, M. Henderson, M. Soutto, G. M. Davis, A. G. McLoed, M. J. Townsend, L. H. Glimcher, D. P. Mortlock, T. M. Aune et al.
J. Immunol. 185, 1492-1501 (1 August 2010)

Smad2 and Smad3 Are Redundantly Essential for the TGF-{beta}-Mediated Regulation of Regulatory T Plasticity and Th1 Development
T. Takimoto, Y. Wakabayashi, T. Sekiya, N. Inoue, R. Morita, K. Ichiyama, R. Takahashi, M. Asakawa, G. Muto, T. Mori et al.
J. Immunol. 185, 842-855 (15 July 2010)

Naturally Activated V{gamma}4 {gamma}{delta} T Cells Play a Protective Role in Tumor Immunity through Expression of Eomesodermin
W. He, J. Hao, S. Dong, Y. Gao, J. Tao, H. Chi, R. Flavell, R. L. O'Brien, W. K. Born, J. Craft et al.
J. Immunol. 185, 126-133 (1 July 2010)

Distinct Roles for IL-2 and IL-15 in the Differentiation and Survival of CD8+ Effector and Memory T Cells
D. M. Mitchell, E. V. Ravkov, and M. A. Williams
J. Immunol. 184, 6719-6730 (15 June 2010)

{gamma}c deficiency precludes CD8+ T cell memory despite formation of potent T cell effectors
H. Decaluwe, M. Taillardet, E. Corcuff, I. Munitic, H. K. W. Law, B. Rocha, Y. Riviere, and J. P. Di Santo
Proc. Natl. Acad. Sci. USA 107, 9311-9316 (18 May 2010)

Pharmacologic Induction of CD8+ T Cell Memory: Better Living Through Chemistry
L. Gattinoni, C. A. Klebanoff, and N. P. Restifo
Sci Transl Med 1, 11ps12-11ps12 (16 December 2009)

Interplay between Chromatin Remodeling and Epigenetic Changes during Lineage-Specific Commitment to Granzyme B Expression
T. Juelich, E. Sutcliffe, A. Denton, Y. He, P. C. Doherty, C. Parish, S. J. Turner, D. Tremethick, and S. Rao
J. Immunol. 183, 7063-7072 (1 December 2009)

Kinetics of the Immune Response Profile in Guinea Pigs after Vaccination with Mycobacterium bovis BCG and Infection with Mycobacterium tuberculosis
A. Grover, J. Taylor, J. Troudt, A. Keyser, K. Arnett, L. Izzo, D. Rholl, and A. Izzo
Infect. Immun. 77, 4837-4846 (1 November 2009)

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