Coordinated expansion of both memory T cells and NK cells in response to CMV infection in humans

Bayard, Charles; Lepetitcorps, Hélène; Roux, Antoine; Larsen, Martin; Fastenackels, Solène; Salle, V.; Vieillard, Vincent; Marchant, Arnaud; Stern, M.; Boddaert, Jacques; Bajolle, Fanny; Appay, Victor; Sauce, Delphine

doi:10.1002/eji.201546179

Cited by 57 publications

(46 citation statements)

References 54 publications

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“…Previously published data [21][22] have shown that high CD57 expression levels, co-expressed with NKG2C, on CD56 dim NK cells, define a terminal maturational step for CD56 dim NK cells and depict a human viral memory NK cell subset, which lacks in NK cells derived from patients with mutations in NFKB1. Exposure to CMV has been shown to up-regulate CD57 and NKG2C on human NK cells [23][24]. Within this cohort of patents, only one patient presented an infection from CMV.…”

Section: Discussionmentioning

confidence: 90%

NFKB1 regulates human NK cell maturation and effector functions

Lougaris

Patrizi

Baronio

et al. 2017

Clinical Immunology

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NFKB1, a component of the canonical NF-κB pathway, was recently reported to be mutated in a limited number of CVID patients. CVID-associated mutations in NFKB2 (non-canonical pathway) have previously been shown to impair NK cell cytotoxic activity. Although a biological function of NFKB1 in non-human NK cells has been reported, the role of NFKB1 mutations for human NK cell biology and disease has not been investigated yet. We decided therefore to evaluate the role of monoallelic NFKB1 mutations in human NK cell maturation and functions. We show that NFKB1 mutated NK cells present impaired maturation, defective cytotoxicity and reduced IFN-γ production upon in vitro stimulation. Furthermore, human IL-2 activated NFKB1 mutated NK cells fail to upregulate the expression of the activating marker NKp44 and show reduced proliferative capacity. These data suggest that NFKB1 plays an essential novel role for human NK cell maturation and effector functions.

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Section: Discussionmentioning

confidence: 90%

NFKB1 regulates human NK cell maturation and effector functions

Lougaris

Patrizi

Baronio

et al. 2017

Clinical Immunology

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“…There seem to be limited age-related changes in KIR and NKG2 repertoires of NK cells. A decrease in NKG2A expression occurs from young to elderly adults [104,105]. In contrast, an increased frequency of KIR expression was observed in NK cells from cord blood to adults without any further increases in the elderly [98].…”

Section: Natural Killer Cells: Changes In Their Subsetsmentioning

confidence: 86%

Aging of the immune system: Focus on inflammation and vaccination

et al. 2016

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Major advances in preventing, delaying or curing individual pathologies are responsible for an increasingly long life span in the developed parts of our planet, and indeed reaching 8–9 decades of life is nowadays extremely frequent. However, medical and sanitary advances have not prevented or delayed the underlying cause of the disparate pathologies occurring in the elderly: aging itself. The identification of the basis of the aging processes that drives the multiple pathologies and loss of function typical of older individuals is a major challenge in current aging research. Among the possible causes, an impairment of the immune system plays a major role, and indeed numerous studies have described immunological changes which occur with age. Far from the intention of being exhaustive, this review will focus on recent advances and views on the role that modifications of cell signalling and remodelling of the immune response play during human aging and longevity, paying particular attention to phenomena which are linked to the so called inflammaging process, such as dysregulation of innate immunity, altered T-cell or B-cell maturation and differentiation, as well as to the implications of immune aging for vaccination strategies in the elderly.

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“…Indeed, highly differentiated mature CD57 C CD56 C CD16 C NK cells accumulated with aging (in particular in CMV seropositive donors). [56][57][58] In HIV patients, it is their functionality which is modified: these cells display a decreased ability to kill virus-infected target cells and to interact with other cellular components of the adaptive immune system. 59,60 During chronic HIV infection, there is an impairment of NK cell cytotoxicity and cytokine secretion as well as a reduced capacity to respond to IFN-a and to produce high amounts of IFN-g and TNF a along with low amounts of perforin.…”

Section: Gradual Loss Of the Cd56mentioning

confidence: 99%

Assessing immune aging in HIV-infected patients

Appay

Sauce

2016

Virulence

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Many of the alterations that affect innate and adaptive immune cell compartments in HIV-infected patients are reminiscent of the process of immune aging, characteristic of old age. These alterations define the immunological age of individuals and are likely to participate to the decline of immune competence with HIV disease progression. It is therefore important to characterize these changes, which point toward the accumulation of highly differentiated immunocompetent cells, associated with overall telomere length shortening, as well as understanding their etiology, especially related to the impact of chronic immune activation. Particular attention should be given to the exhaustion of primary immune resources, including haematopoietic progenitors and na€ ıve cells, which holds the key for effective hematopoiesis and immune response induction, respectively. The alteration of these compartments during HIV infection certainly represents the foundation of the immune parallel with aging.

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Coordinated expansion of both memory T cells and NK cells in response to CMV infection in humans

Abstract: NK cells are key players in the fight against persistent viruses. Human cytomegalovirus (HCMV) infection is associated with the presence of a population of CD16

Cited by 57 publications

References 54 publications

NFKB1 regulates human NK cell maturation and effector functions

NFKB1 regulates human NK cell maturation and effector functions

Aging of the immune system: Focus on inflammation and vaccination

Assessing immune aging in HIV-infected patients

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