Effect of age and latent CMV infection on CD8+ CD56+ T cells (NKT-like) frequency and functionality

Hassouneh, Fakhri; Campos, Carmen; López-Sejas, Nelson; Alonso, Corona; Tarazona, Raquel; Solana, Rafael; Pera, Alejandra

doi:10.1016/j.mad.2015.12.003

Cited by 22 publications

(23 citation statements)

References 52 publications

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“…Interestingly, it has also been shown that the expression of CD161 in CMV-specific cytotoxic T lymphocytes is very low (71). Considering the inhibitory capacity of CD161 on NK and T lymphocytes cytokine production, these results support that the CMV-induced downregulation of CD161 receptor together with the expansion of polyfunctional response of CD57 + NK cells and T- and NKT-like lymphocytes (14, 30, 69, 72, 73), contribute to the proinflammatory environment observed in CMV-seropositive healthy individuals.…”

Section: Discussionsupporting

confidence: 65%

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: Discussionsupporting

confidence: 65%

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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“…Even though pronounced memory inflation is thought to result in the accumulation of dysfunctional CMV-specific T cells, several studies have shown that HCMV-specific CD8 + T cells are polyfunctional in young and middle-aged hosts and can produce multiple cytokines and induce strong effector immune responses to staphylococcal enterotoxin B (SEB) (Solana et al, 2012a; Pera et al, 2014; Sansoni et al, 2014; Hassouneh et al, 2016). With increasing age, T cell exhaustion, another form of T cell dysfunction, can arise during chronic viral infections, such as with HIV, in which T cells are constantly stimulated by highly replicating viruses (Wherry, 2011).…”

Section: Human CMV Infection Memory Inflation and Immunosenescencementioning

confidence: 99%

Mechanisms Underlying T Cell Immunosenescence: Aging and Cytomegalovirus Infection

2016

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The ability of the human immune system to protect against infectious disease declines with age and efficacy of vaccination reduces significantly in the elderly. Aging of the immune system, also termed as immunosenescence, involves many changes in human T cell immunity that is characterized by a loss in naïve T cell population and an increase in highly differentiated CD28- memory T cell subset. There is extensive data showing that latent persistent human cytomegalovirus (HCMV) infection is also associated with age-related immune dysfunction in the T cells, which might enhance immunosenescence. Understanding the molecular mechanisms underlying age-related and HCMV-related immunosenescence is critical for the development of effective age-targeted vaccines and immunotherapies. In this review, we will address the role of both aging and HCMV infection that contribute to the T cell senescence and discuss the potential molecular mechanisms in aged T cells.

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“…These above-referenced studies highlight the existence of functional heterogeneity among the CD8 + T-cell memory subsets. Regarding NK-like CD8 + T cells, high percentages of these cells also express the CD57 marker and likewise arise after CMV infection (10). It has been well established that NK-like CD8 + T-cells expand with age (30, 37–39) and some studies suggest that their frequency is increased in CMV-seropositive individuals (40–42).…”

Section: Nk-like Cd8+ T-cells In Virus Infection and Immunosenescencementioning

confidence: 99%

“…However, recent work performed in healthy young individuals indicates that NK-like CD8 + T-cell frequency is not affected by CMV latent infection. Thus, the authors propose that these cells accumulate with age in the CMV-seropositive individuals, rather than with CMV infection per se (10). …”

Section: Nk-like Cd8+ T-cells In Virus Infection and Immunosenescencementioning

confidence: 99%

“…Natural killer-like CD8 + T-cells have been described using different names, for example: CD56 + CD8 + NKT-like cells (10), CD28 − KIR + CD8 + T-cells (5), KIR + CD8 + T-cells—particularly those expressing NKG2A—(11), or the general term innate CD8 + T-cells—since NKR + αβT-cells likely represent immune effector cells that are capable of combining innate and adaptive functions (12). Table 1 summarizes the most relevant information regarding the characterization of NK-like CD8 + T-cells.…”

Section: Introductionmentioning

confidence: 99%

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Adaptive Memory of Human NK-like CD8+ T-Cells to Aging, and Viral and Tumor Antigens

2016

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Human natural killer (NK)-like CD8+ T-cells are singular T-cells that express both T and NK cell markers such as CD56; their frequencies depend on their differentiation and activation during their lifetime. There is evidence of the presence of these innate CD8+ T-cells in the human umbilical cord, highlighting the necessity of investigating whether the NK-like CD8+ T-cells arise in the early stages of life (gestation). Based on the presence of cell surface markers, these cells have also been referred to as CD8+KIR+ T-cells, innate CD8+ T-cells, CD8+CD28−KIR+ T-cells or NKT-like CD8+CD56+ cells. However, the functional and co-signaling significance of these NK cell receptors on NK-like CD8+ T-cells is less clear. Also, the diverse array of costimulatory and co-inhibitory receptors are spatially and temporally regulated and may have distinct overlapping functions on NK-like CD8+ T-cell priming, activation, differentiation, and memory responses associated with different cell phenotypes. Currently, there is no consensus regarding the functional properties and phenotypic characterization of human NK-like CD8+ T-cells. Environmental factors, such as aging, autoimmunity, inflammation, viral antigen re-exposure, or the presence of persistent tumor antigens have been shown to allow differentiation (“adaptation”) of the NK-like CD8+ T-cells; the elucidation of this differentiation process and a greater understanding of the characteristics of these cells could be important for their eventual in potential therapeutic applications aimed at improving protective immunity. This review will attempt to elucidate an understanding of the characteristics of these cells with the goal toward their eventual use in potential therapeutic applications aimed at improving protective immunity.

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Effect of age and latent CMV infection on CD8+ CD56+ T cells (NKT-like) frequency and functionality

Cited by 22 publications

References 52 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

Mechanisms Underlying T Cell Immunosenescence: Aging and Cytomegalovirus Infection

Adaptive Memory of Human NK-like CD8+ T-Cells to Aging, and Viral and Tumor Antigens

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