NFκB-Pim-1-Eomesodermin axis is critical for maintaining CD8 T-cell memory quality.
Karin M. Knudson,Karin M. Knudson,Curtis J. Pritzl,Vikas Saxena,Amnon Altman,Mark A. Daniels,Emma Teixeiro +6 more
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TLDR
It is shown that in T cells transitioning to memory, the expression of high levels of Eomes is not constitutive but rather requires a continuum of cell-intrinsic NFκB signaling, which regulates Eomes levels to maintain memory fitness.Abstract:
T-cell memory is critical for long-term immunity. However, the factors involved in maintaining the persistence, function, and phenotype of the memory pool are undefined. Eomesodermin (Eomes) is required for the establishment of the memory pool. Here, we show that in T cells transitioning to memory, the expression of high levels of Eomes is not constitutive but rather requires a continuum of cell-intrinsic NFκB signaling. Failure to maintain NFκB signals after the peak of the response led to impaired Eomes expression and a defect in the maintenance of CD8 T-cell memory. Strikingly, we found that antigen receptor [T-cell receptor (TCR)] signaling regulates this process through expression of the NFκB-dependent kinase proviral integration site for Moloney murine leukemia virus-1 (PIM-1), which in turn regulates NFκB and Eomes. T cells defective in TCR-dependent NFκB signaling were impaired in late expression of Pim-1, Eomes, and CD8 memory. These defects were rescued when TCR-dependent NFκB signaling was restored. We also found that NFκB-Pim-1 signals were required at memory to maintain memory CD8 T-cell longevity, effector function, and Eomes expression. Hence, an NFκB-Pim-1-Eomes axis regulates Eomes levels to maintain memory fitness.read more
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References
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TL;DR: It is shown that mTOR (mammalian target of rapamycin, also known as FRAP1) is a major regulator of memory CD8 T-cell differentiation, and in contrast to what was expected, the immunosuppressive drug Rapamycin has immunostimulatory effects on the generation of memoryCD8 T cells.
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Transcriptional control of effector and memory CD8 + T cell differentiation
Susan M. Kaech,Weiguo Cui +1 more
TL;DR: Over the past decade, the signalling pathways and transcriptional programmes that regulate the formation of heterogeneous populations of effector and memory CD8+ T cells have started to be characterized, and this Review discusses the major advances in these areas.
Journal ArticleDOI
Effector and memory CD8 + T cell fate coupled by T-bet and eomesodermin
Andrew M. Intlekofer,Naofumi Takemoto,E. John Wherry,E. John Wherry,Sarah A. Longworth,John T Northrup,Vikram R. Palanivel,Alan C. Mullen,Christopher R Gasink,Susan M. Kaech,Susan M. Kaech,Joseph D. Miller,Laurent Gapin,Kenneth Ryan,Andreas Russ,Tullia Lindsten,Jordan S. Orange,Ananda W. Goldrath,Ananda W. Goldrath,Rafi Ahmed,Steven L. Reiner +20 more
TL;DR: These key transcription factors T-bet and eomesodermin link the long-term renewal of memory CD8+ T cells to their characteristic effector potency, and are responsible for inducing enhanced expression of CD122, the receptor specifying interleukin 15 responsiveness.