Effector and memory CD8 super(+) T cell fate coupled by T-bet and eomesodermin

• Published in: Nature Immunology 2005-12, Vol.6 (12), p.1236-1244
• Main Authors: Intlekofer, Andrew M, Takemoto, Naofumi, Wherry, E John, Longworth, Sarah A, Northrup, John T, Palanivel, Vikram R, Mullen, Alan C, Gasink, Christopher R, Kaech, Susan M, Miller, Joseph D, Gapin, Laurent, Ryan, Kenneth, Russ, Andreas P, Lindsten, Tullia, Orange, Jordan S, Goldrath, Ananda W, Ahmed, Rafi, Reiner, Steven L
• Format: Article
• Language: English
• ISSN: 1529-2908; 1365-2567
• DOI: 10.1038/ni1268

Two seemingly unrelated hallmarks of memory CD8 super(+) T cells are cytokine- driven proliferative renewal after pathogen clearance and a latent effector program in anticipation of rechallenge. Memory CD8 super(+) 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 super(+) 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 super(+) 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 super(+) 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.