Nature Immunology 6, 1236 - 1244 (2005)
Published online: 6 November 2005; Corrected online: 13 November 2005 | doi:10.1038/ni1268
Effector and memory CD8+ T cell fate coupled by T-bet and eomesoderminAndrew M Intlekofer1, Naofumi Takemoto1, E John Wherry4, 8, Sarah A Longworth1, John T Northrup1, Vikram R Palanivel1, Alan C Mullen1, Christopher R Gasink1, Susan M Kaech4, 8, Joseph D Miller4, Laurent Gapin5, Kenneth Ryan2, Andreas P Russ6, Tullia Lindsten3, Jordan S Orange2, Ananda W Goldrath7, 8, Rafi Ahmed4
& Steven L Reiner11
Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. 2
Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. 3
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. 4
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA. 5
Integrated Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Science Center, Denver, Colorado 80206, USA. 6
Genetics Unit, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. 7
Section on Immunology and Immunogenetics, Joslin Diabetes Center and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA. 8
Present addresses: The Wistar Institute, Philadelphia, Pennsylvania 19104, USA (E.J.W.), Yale University, New Haven, Connecticut 06520, USA (S.M.K.) and University of California, San Diego, La Jolla, California 92093, USA (A.W.G.).
Correspondence should be addressed to Steven L Reiner sreiner@mail.med.upenn.edu Two seemingly unrelated hallmarks of memory CD8+ T cells are cytokine-driven proliferative renewal after pathogen clearance and a latent effector program in anticipation of rechallenge. Memory CD8+ T cells and natural killer cells share cytotoxic potential and dependence on the growth factor interleukin 15. We now show that mice with compound mutations of the genes encoding the transcription factors T-bet and eomesodermin were nearly devoid of several lineages dependent on interleukin 15, including memory CD8+ T cells and mature natural killer cells, and that their cells had defective cytotoxic effector programming. Moreover, T-bet and eomesodermin were responsible for inducing enhanced expression of CD122, the receptor specifying interleukin 15 responsiveness. Therefore, these key transcription factors link the long-term renewal of memory CD8+ T cells to their characteristic effector potency.*Note: In the version of this article initially published online, the third sentence of the abstract was incorrect. The correct sentence is as follows: "We now show that mice with compound mutations of the genes encoding the transcription factors T-bet and eomesodermin were nearly devoid of several lineages dependent on interleukin 15, including memory CD8+ T cells and mature natural killer cells, and that their cells had defective cytotoxic effector programming." The error has been corrected for the HTML and print versions of the article. Additionally, in the print version of this article and the version initially published online, some labels for Tbx21 in Figure 7b are incorrect. This correction has been appended to the PDF version.
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