Independent skewing of the T cell and NK cell compartments associated with cytomegalovirus infection suggests division of labor between innate and adaptive immunity

Bengnér, Malin; Béziat, Vivien; Ernerudh, Jan; Nilsson, Bengt J.; Löfgren, Sture; Wikby, Anders; Malmberg, Karl‐Johan; Strindhall, Jan

doi:10.1007/s11357-013-9587-y

Cited by 13 publications

(13 citation statements)

References 44 publications

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“…CD57+ NK cells and CD8+ T cells were found in a well-defined cohort of elderly people, concluding that both events were in general non-overlapping and independent (35). On the other hand, an inverse relationship between NK and T-cell responses to HCMV was detected in younger blood donors (36).…”

Section: In This Regard Some Studies Have Directly Addressed the Relmentioning

confidence: 87%

Development of the adaptive NK cell response to human cytomegalovirus in the context of aging

López‐Botet

Muntasell

Martínez-Rodríguez

et al. 2016

Mechanisms of Ageing and Development

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Human cytomegalovirus (HCMV) establishes a highly prevalent life-long latent infection. Though generally subclinical, HCMV infection may have severe consequences during fetal development and in immunocompromised individuals. Based on epidemiological studies HCMV(+) serology has been associated with the development of atherosclerosis, immune senescence and an increase mortality rate in elderly people. Such long-term detrimental effects of the viral infection presumably result from an inefficient immune control of the pathogen, depending on the quality and evolution of the individual host-pathogen relationship. Together with antigen-specific T lymphocytes, NK cells play an important role in anti-viral immune defense. HCMV promotes in some individuals the differentiation and persistent steady state expansion of an NK cell subset bearing the CD94/NKG2C activating receptor. The relationship between this adaptive NK cell response to HCMV and aging is overviewed.

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Section: In This Regard Some Studies Have Directly Addressed the Relmentioning

confidence: 87%

Development of the adaptive NK cell response to human cytomegalovirus in the context of aging

López‐Botet

Muntasell

Martínez-Rodríguez

et al. 2016

Mechanisms of Ageing and Development

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“…In particular, the levels of pretransplant CMV-specific TcRab + T cells have been reported to predict the risk for posttransplant infection (6,35), and increased numbers of TcRgd + T cells were associated with CMV control (36). Recent reports support that adaptive NK cells and Ag-specific T cells may develop independently in response to CMV (37,38), and further studies are warranted to evaluate their relative contribution to the control of the viral infection in KTRs.…”

Section: Discussionmentioning

confidence: 99%

Adaptive NKG2C+ NK Cell Response and the Risk of Cytomegalovirus Infection in Kidney Transplant Recipients

Redondo-Pachón

Crespo

Yélamos

et al. 2017

The Journal of Immunology

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CMV infection in kidney transplant recipients (KTRs) has been associated with an increased risk for graft loss and reduced host survival. CMV promotes persistent expansions of NK cells expressing the CD94/NKG2C receptor. The NKG2C (KLRC2) gene is frequently deleted, and copy number influences the adaptive response of NKG2C NK cells. The distribution of NKG2C NK cells and NKG2C genotypes (NKG2C, NKG2C, NKG2C) were studied in cross-sectional (n = 253) and prospective (n = 122) KTR cohorts. Assessment of CMV viremia was restricted to symptomatic cases in the retrospective study, but was regularly monitored in the prospective cohort. Overall, the proportions of NKG2C NK cells were significantly higher in KTRs who had suffered posttransplant symptomatic CMV infection in the cross-sectional study. Yet, along the prospective follow-up (3, 6, 12, and 24 mo), posttransplant NKG2C NK cell expansions were not observed in every patient with detectable viremia who received preemptive antiviral therapy, suggesting that the adaptive NK cell response may be inversely related with the degree of CMV control. Remarkably, the incidence of posttransplant viremia was reduced among cases with high pretransplant levels of NKG2C NK cells. The NKG2C genotype distribution was comparable in KTR and healthy controls, and greater proportions of NKG2C cells were detected in NKG2C than in NKG2C patients. Yet, a trend toward increased NKG2C and reduced NKG2C frequencies associated with symptomatic infection was appreciated in both cohorts. Altogether, our results indirectly support that adaptive NKG2C NK cells are involved in the control of CMV in KTRs.

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“…Thus, similar mechanisms may also play a role with respect to NK cells. NK cell maturation has been also observed in other viral diseases such as infection with the cytomegalovirus (CMV) and, thus, is not specific to HIV(+) individuals[47,58]. In HCV mono-infected patients, however, such a mechanism seems to be of minor if any relevance because the NK cell maturation status did not differ significantly from that found in healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Alterations of the NK cell pool in HIV/HCV co-infection

et al. 2017

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BackgroundA relevant proportion of human immunodeficiency virus (HIV) infected patients is co-infected with the hepatitis C virus (HCV). HCV co-infection in HIV-positive patients is associated with faster progression of liver disease in comparison to HCV mono-infection. Natural killer (NK) cells critically modulate the natural course of HCV infection. Both HIV and HCV mono-infection are associated with alterations of the NK cell pool. However, little data is available concerning phenotype and function of NK cells in HIV/HCV co-infection.MethodsA total of 34 HIV/HCV co-infected, 35 HIV and 39 HCV mono-infected patients and 43 healthy control persons were enrolled into this study. All HIV-positive patients were under effective antiretroviral therapy. NK cell phenotype, IFN-γ production and degranulation were studied by flow cytometry.ResultsNK cell frequency in HIV/HCV co-infection was significantly lower than in healthy individuals but did not differ from HIV and HCV mono-infection. HIV/HCV co-infection was associated with significantly decreased expression of the maturation/differentiation markers CD27/62L/127 on NK cells but increased expression of CD57 compared to healthy controls. Of note, expression also differed significantly from HCV mono-infection but was similar to HIV mono-infection, suggesting a pronounced impact of HIV on these alterations. Similar findings were made with regard to the NK cell receptors NKG2A/C and NKp30. More importantly, NK cells in co-infection displayed a highly impaired functional activity with significantly lower IFN-γ production and degranulation than in healthy donors as well as HIV and HCV mono-infection, suggesting a synergistic effect of both viruses.ConclusionsOur data indicate that HIV/HCV co-infection is associated with significant alterations of the NK cell pool, which might be involved in the rapid progression of liver disease in co-infected patients and which mainly reflect alterations observed in HIV mono-infection.

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Independent skewing of the T cell and NK cell compartments associated with cytomegalovirus infection suggests division of labor between innate and adaptive immunity

Cited by 13 publications

References 44 publications

Development of the adaptive NK cell response to human cytomegalovirus in the context of aging

Development of the adaptive NK cell response to human cytomegalovirus in the context of aging

Adaptive NKG2C+ NK Cell Response and the Risk of Cytomegalovirus Infection in Kidney Transplant Recipients

Alterations of the NK cell pool in HIV/HCV co-infection

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