Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin.

Andrew M Intlekofer; Naofumi Takemoto; E John Wherry; Sarah A Longworth; John T Northrup; Vikram R Palanivel; Alan C Mullen; Christopher R Gasink; Susan M Kaech; Joseph D Miller; Laurent Gapin; Kenneth Ryan; Andreas P Russ; Tullia Lindsten; Jordan S Orange; Ananda W Goldrath; Rafi Ahmed; Steven L Reiner

doi:10.1038/ni1268

PubMed · 16273099

Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin.

Andrew M Intlekofer·Naofumi Takemoto·E John Wherry·Sarah A Longworth·John T Northrup·Vikram R Palanivel·Alan C Mullen·Christopher R Gasink·Susan M Kaech·Joseph D Miller·Laurent Gapin·Kenneth Ryan·Andreas P Russ·Tullia Lindsten·Jordan S Orange·Ananda W Goldrath·Rafi Ahmed·Steven L Reiner

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Abstract

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.

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Animals CD8-Positive T-Lymphocytes Cells, Cultured Humans Immunologic Memory Interleukin-15 Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Phenotype Receptors, Interleukin-2 T-Box Domain Proteins Transcription Factors T-bet Transcription Factor Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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Andrew M Intlekofer, Naofumi Takemoto, E John Wherry, Sarah A Longworth, John T Northrup, Vikram R Palanivel, Alan C Mullen, Christopher R Gasink, Susan M Kaech, Joseph D Miller, Laurent Gapin, Kenneth Ryan, Andreas P Russ, Tullia Lindsten, Jordan S Orange, Ananda W Goldrath, Rafi Ahmed, Steven L Reiner. 2005-11-06. Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin.. https://doi.org/10.1038/ni1268

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