T-bet and Eomesodermin in NK Cell Development, Maturation, and Function

Simonetta, Federico; Pradier, Amandine; Roosnek, Eddy

doi:10.3389/fimmu.2016.00241

Cited by 112 publications

(110 citation statements)

References 47 publications

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“…Recent reports have strengthened the significance of T-bet and Eomes in NK cell biology (47). In mice, T-bet and Eomes are necessary for maintenance of peripheral NK cells, their deletion in mature NK cells results in reversion to an immature phenotype (46).…”

Section: Discussionmentioning

confidence: 96%

“…It has been observed that the frequency of T-bet + cells and the level of T-bet expression per cell is significantly greater in the CD56 dim population compared to the CD56 bright population from peripheral human immune cells, contrary to Eomes expression pattern, suggesting the existence of a relationship among the expression levels of both transcription factors and the functionality of these cells (45). Thus, T-bet is related to terminal stages of maturation, while Eomes is downregulated during peripheral maturation (47). …”

Section: Introductionmentioning

confidence: 99%

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Effect of CMV and Aging on the Differential Expression of CD300a, CD161, T-bet, and Eomes on NK Cell Subsets

et al. 2016

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Natural killer (NK) cells are innate lymphoid cells involved in the defense against virus-infected cells and tumor cells. NK cell phenotype and function is affected with age and cytomegalovirus (CMV) latent infection. Aging affects the frequency and phenotype of NK cells, and CMV infection also contributes to these alterations. Thus, a reduction of CD56bright NK cell subpopulation associated with age and an expansion of memory-like NK cells CD56dimCD57+NKG2C+ probably related to CMV seropositivity have been described. NK cells express T-bet and Eomes transcription factors that are necessary for the development of NK cells. Here, we analyze the effect of age and CMV seropositivity on the expression of CD300a and CD161 inhibitory receptors, and T-bet and Eomes transcription factors in NK cell subsets defined by the expression of CD56 and CD57. CD300a is expressed by the majority of NK cells. CD56bright NK cells express higher levels of CD300a than CD56dim NK cells. An increase in the expression of CD300a was associated with age, whereas a decreased expression of CD161 in CD56dim NK cells was associated with CMV seropositivity. In CD56dim NK cells, an increased percentage of CD57+CD300a+ and a reduction in the percentage of CD161+CD300a+ cells were found to be associated with CMV seropositivity. Regarding T-bet and Eomes transcription factors, CMV seropositivity was associated with a decrease of T-bethi in CD56dimCD57+ NK cells from young individuals, whereas Eomes expression was increased with CMV seropositivity in both CD56bright and CD56dimCD57+/− (from middle age and young individuals, respectively) and was decreased with aging in all NK subsets from the three group of age. In conclusion, CMV infection and age induce significant changes in the expression of CD300a and CD161 in NK cell subsets defined by the expression of CD56 and CD57. T-bet and Eomes are differentially expressed on NK cell subsets, and their expression is affected by CMV latent infection and aging.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Effect of CMV and Aging on the Differential Expression of CD300a, CD161, T-bet, and Eomes on NK Cell Subsets

et al. 2016

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“…In mice, these two ILC subsets appear to be developmentally distinct (6), because in addition to these CHILP data described above, genetic fate-mapping (fm) studies for Rorc2 , which encodes Rorγt, showed that mouse ILC3s are Rorc2 fm + whereas mouse Eomes + NK cells are Rorc2 fm − (68, 71, 72). In contrast, Scoville et al recently demonstrated that the putative human CILP (SLT stage 2b) population expresses RORγt and that human PB CD56 bright NK cells, which are NKp80 + EOMES + (4, 40, 59, 73, 74), constitutively express detectable RORC2 transcript (42). Thus, as opposed to mouse NK cells, at least some human NK cells would be fm + for RORC2 if such an experiment could be performed.…”

Section: Modeling Human Nk Cell Development In the Context And Era Ofmentioning

confidence: 93%

Modeling Human Natural Killer Cell Development in the Era of Innate Lymphoid Cells

2017

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Decades after the discovery of natural killer (NK) cells, their developmental pathways in mice and humans have not yet been completely deciphered. Accumulating evidence indicates that NK cells can develop in multiple tissues throughout the body. Moreover, detailed and comprehensive models of NK cell development were proposed soon after the turn of the century. However, with the recent identification and characterization of other subtypes of innate lymphoid cells (ILCs), which show some overlapping functional and phenotypic features with NK cell developmental intermediates, the distinct stages through which human NK cells develop from early hematopoietic progenitor cells remain unclear. Thus, there is a need to reassess and refine older models of NK cell development in the context of new data and in the era of ILCs. Our group has focused on elucidating the developmental pathway of human NK cells in secondary lymphoid tissues (SLTs), including tonsils and lymph nodes. Here, we provide an update of recent progress that has been made with regard to human NK cell development in SLTs, and we discuss these new findings in the context of contemporary models of ILC development.

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“…Most cNK cells in PB are CD56 dim , whereas CD56 bright cNK cells represent the minority of cNK cells in healthy donor PB, usually constituting ≤15% of the total circulating cNK cell pool (defined as Lin − CD56 + ). In healthy individuals, both PB cNK cell subsets constitutively express similar amounts of various intracellular and surface factors including T-BET, EOMES, the common IL-2 and IL-15 receptor beta chain (IL-2/15Rβ, CD122), 2B4, DNAM-1, NKG2D, NKp30, and NKp80 (Caligiuri, 2008; Collins et al, 2017; Lanier, 1998; Moretta et al, 2014; Simonetta et al, 2016). Moreover, in a general sense both subsets show the characteristic functions of cNK cells; i.e.…”

Section: The Breadth Of Human Nk Cell Diversitymentioning

confidence: 99%

The Broad Spectrum of Human Natural Killer Cell Diversity

et al. 2017

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SUMMARY Natural killer (NK) cells provide protection against infectious pathogens and cancer. For decades it has been appreciated that two major NK cell subsets (CD56bright and CD56dim) exist in humans and have distinct anatomical localization patterns, phenotypes, and functions in immunity. In light of this traditional NK cell dichotomy, it is now clear that the spectrum of human NK cell diversity is much broader than originally appreciated as a result of variegated surface receptor, intracellular signaling molecule, and transcription factor expression; tissue-specific imprinting; and foreign antigen exposure. The recent discoveries of tissue-resident NK cell developmental intermediates, non-NK innate lymphoid cells, and the capacity for NK cells to adapt and differentiate into long-lived memory cells has added further complexity to this field. Here we review our current understanding of the breadth and generation of human NK cell diversity.

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T-bet and Eomesodermin in NK Cell Development, Maturation, and Function

Cited by 112 publications

References 47 publications

Effect of CMV and Aging on the Differential Expression of CD300a, CD161, T-bet, and Eomes on NK Cell Subsets

Effect of CMV and Aging on the Differential Expression of CD300a, CD161, T-bet, and Eomes on NK Cell Subsets

Modeling Human Natural Killer Cell Development in the Era of Innate Lymphoid Cells

The Broad Spectrum of Human Natural Killer Cell Diversity

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