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

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

doi:10.1038/ni1268

Cited by 1,078 publications

(1,233 citation statements)

References 47 publications

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“…Co‐expression of the transcription factors T‐bet and Eomes is critical for the cytotoxic functions of both CD8+ T‐cells and NK cells,44, 106 and the similarities in granzyme and perforin expression in these cells is reflected by their expression of the T‐bet and Eomes. Thus, both CD56 dim NK cells and CD161+ CD8+ T‐cells are enriched for Eomes+T‐bet high cells,16, 107 while CD56 bright NK cells have an Eomes+T‐bet low phenotype,107 which is mirrored by CD8+ MAIT cells 108.…”

Section: Functional Similarities Between Nk Cell and Cd8+ T‐cell Subsetsmentioning

confidence: 99%

Innate‐like CD8+ T‐cells and NK cells: converging functions and phenotypes

2018

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SummaryNew data in the worlds of both innate‐like CD8+ T‐cells and natural killer (NK) cells have, in parallel, clarified some of the phenotypes of these cells and also their associated functions. While these cells are typically viewed entirely separately, the emerging innate functions of T‐cells and, similarly, the adaptive functions of NK cells suggest that many behaviours can be considered in parallel. In this review we compare the innate functions of CD8+ T‐cells (especially mucosal‐associated invariant T‐cells) and those of NK cells, and how these relate to expression of phenotypic markers, especially CD161 and CD56.

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Section: Functional Similarities Between Nk Cell and Cd8+ T‐cell Subsetsmentioning

confidence: 99%

Innate‐like CD8+ T‐cells and NK cells: converging functions and phenotypes

2018

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“…In addition to Th1 cells, T-bet is detected in several other immune cells, including CD8 ϩ T cells (3,5,6), dendritic cells (7), B cells (8), NK cells and NKT cells (9 -11). T-bet regulates expression of numerous immune systemassociated genes, including cytokines (4), cytokine receptors (9 -12), chemokines (7,11), chemokine receptors (4,11,13) and cytotoxicity (9,11). Altogether these results have established T-bet as an essential transcription factor in the generation and regulation of proper immune responses.…”

Section: Temporal Dissection Of T-bet Functionsmentioning

confidence: 99%

“…We reported previously that ectopic expression of T-bet in T-bet Ϫ/Ϫ NKT cells induces expression of IL-2/IL-15R␤ (CD122) mRNA and cell surface expression of CD122 (10,11). Furthermore, recent data have emphasized the critical role of T-bet and its homolog Eomes in enhancing CD122 expression and consequently in controlling the survival of IL-15-dependent cells, including NKT, NK, and CD8 memory cells (9). In addition, T-bet has been involved in the control of Th1 cell migration to inflammatory sites through its regulation of expression of the chemokine receptor CxCR3 (11,13).…”

Section: Delayed Induction Of T-bet Activity In Developing Th2 Cells mentioning

confidence: 99%

Temporal Dissection of T-bet Functions

Matsuda

George²,

Hagman

et al. 2007

The Journal of Immunology

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T-bet is a transcription factor of the T-box family that regulates the expression of numerous immune system-associated genes. T-bet directs the acquisition of the Th1-associated genetic program in differentiating CD4+ lymphocytes. It also influences the development of NK and NKT cells through its regulation of the IL-2/IL-15Rβ-chain (CD122) and the trafficking of these lymphocytes through CxCR3. The temporal requirements of T-bet activity for the production of IFN-γ and the regulation of CD122 and CxCR3 expression remain undefined. We produced an ectopically controllable form of T-bet by fusing its C-terminal domain with a mutated ligand-binding domain of human estrogen receptor α. By temporally controlling the expression of T-bet-estrogen receptor α by the addition or removal of 4-hydroxytamoxifen (4-HT), we show that IFN-γ, CD122, and CxCR3 are direct gene targets of T-bet whose expression are acutely regulated by T-bet activity.

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“…1 These effector T-cell subsets are driven by distinct networks: a transcriptional program involving Blimp1, Id2 and t-bet is critical for the generation of KLRG1 hi CD127 lo effector cells, [1][2][3][4] whereas an alternative transcriptional program involving Bcl-6, STAT3, eomoesodermin, Id3 and T-cell factor-1 are critical for the generation of KLRG1 lo CD127 hi pre-memory cells. [5][6][7][8][9][10] Although these differentiation programs have been used to explain which cells die as effectors and which cells survive and become memory cells, the results are complicated by the fact that little work has been done examining effector CD8 þ T-cell responses in mice whose death programs have been disabled.…”

mentioning

confidence: 99%

Bim controls IL-15 availability and limits engagement of multiple BH3-only proteins

Kurtuluş

Sholl

et al. 2014

Cell Death Differ

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During the effector CD8 þ T-cell response, transcriptional differentiation programs are engaged that promote effector T cells with varying memory potential. Although these differentiation programs have been used to explain which cells die as effectors and which cells survive and become memory cells, it is unclear if the lack of cell death enhances memory. Here, we investigated effector CD8 þ T-cell fate in mice whose death program has been largely disabled because of the loss of Bim. Interestingly, the absence of Bim resulted in a significant enhancement of effector CD8 þ T cells with more memory potential. Bim-driven control of memory T-cell development required T-cell-specific, but not dendritic cell-specific, expression of Bim. Both total and T-cell-specific loss of Bim promoted skewing toward memory precursors, by enhancing the survival of memory precursors, and limiting the availability of IL-15. Decreased IL-15 availability in Bim-deficient mice facilitated the elimination of cells with less memory potential via the additional pro-apoptotic molecules Noxa and Puma. Combined, these data show that Bim controls memory development by limiting the survival of pre-memory effector cells. Further, by preventing the consumption of IL-15, Bim limits the role of Noxa and Puma in causing the death of effector cells with less memory potential.

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

Cited by 1,078 publications

References 47 publications

Innate‐like CD8+ T‐cells and NK cells: converging functions and phenotypes

Innate‐like CD8+ T‐cells and NK cells: converging functions and phenotypes

Temporal Dissection of T-bet Functions

Bim controls IL-15 availability and limits engagement of multiple BH3-only proteins

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