Decreased NK Cell FcRγ in HIV-1 Infected Individuals Receiving Combination Antiretroviral Therapy: a Cross Sectional Study

Leeansyah, Edwin; Zhou, Jingling; Paukovics, Geza; Lewin, Sharon R.; Crowe, Suzanne; Jaworowski, Anthony

doi:10.1371/journal.pone.0009643

Cited by 18 publications

(16 citation statements)

References 30 publications

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“…However, the reported NK cell exhaustion and dysfunction in HIV-infected subjects (38)(39)(40)(41), which only partially normalize after ART, may reduce the effectiveness of Abs with Fc-mediated functions. Further investigation into the Fc␥RIIIa surface expression on autologous NK cells and the TIV-induced autologous NK cell activation in HIV-infected subjects is warranted to help us better understand the effect of HIV infection on NK cell-mediated ADCC after influenza vaccination.…”

Section: Discussionmentioning

confidence: 98%

Antibody Responses with Fc-Mediated Functions after Vaccination of HIV-Infected Subjects with Trivalent Influenza Vaccine

Kristensen

Lay

Ana-Sosa-Batiz

et al. 2016

J Virol

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Section: Discussionmentioning

confidence: 98%

Antibody Responses with Fc-Mediated Functions after Vaccination of HIV-Infected Subjects with Trivalent Influenza Vaccine

Kristensen

Lay

Ana-Sosa-Batiz

et al. 2016

J Virol

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“…65,67 NK cells from treated HIV-infected patients have reduced expression of key signaling proteins that are required for antibody-dependent cellular cytotoxicity; however, the factors causing this phenomenon are unknown. 68 Moreover, virologically suppressed HIV patients show activation of NK cells and persistent innate immune activation. 69 It remains to elucidate if NK cells from elderly people exhibit a similar activation pattern.…”

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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“…We have previously shown that expression of FcRg in NK cells is decreased in HIV-infected individuals receiving cART compared with HIV-uninfected controls (12). We hypothesized that HIVassociated immune activation causes downregulation of FcRg in NK cells, leading to inhibition of ADCC signaling.…”

mentioning

confidence: 97%

“…We have previously reported changes in NK cells purified from HIV patients receiving cART, where expression of key signaling proteins required for Ab-dependent cellular cytotoxicity (ADCC) was substantially reduced (12). NK cells in peripheral blood are commonly defined as belonging to one of two subsets.…”

mentioning

confidence: 99%

Virologically Suppressed HIV Patients Show Activation of NK Cells and Persistent Innate Immune Activation

Lichtfuss

Cheng

Farsakoglu

et al. 2012

The Journal of Immunology

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110

106

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FcRγ is an ITAM-containing adaptor required for CD16 signaling and function in NK cells. We have previously shown that NK cells from HIV patients receiving combination antiretroviral therapy (cART) have decreased FcRγ expression, but the factors causing this are unknown. We conducted a cross-sectional study of cART-naive viremic patients (ART−), virologically suppressed patients receiving cART (ART+), and HIV-uninfected controls. CD8+ T cells were activated, as assessed by CD38+HLA-DR+ expression, in ART− patients (p < 0.0001), which was significantly reduced in ART+ patients (p = 0.0005). In contrast, CD38+HLA-DR+ NK cells were elevated in ART− patients (p = 0.0001) but did not decrease in ART+ patients (p = 0.88). NK cells from both ART− and ART+ patients showed high levels of spontaneous degranulation in ex vivo whole blood assays as well as decreased CD16 expression (p = 0.0001 and p = 0.0025, respectively), FcRγ mRNA (p < 0.0001 for both groups), FcRγ protein expression (p = 0.0016 and p < 0.0001, respectively), and CD16-dependent Syk phosphorylation (p = 0.0001 and p = 0.003, respectively). HIV-infected subjects showed alterations in NK activation, degranulation, CD16 expression and signaling, and elevated plasma markers of inflammation and macrophage activation, that is, neopterin and sCD14, which remained elevated in ART+ patients. Alterations in NK cell measures did not correlate with viral load or CD4 counts. These data show that in HIV patients who achieve viral suppression following cART, NK cell activation persists. This suggests that NK cells respond to factors different from those driving T cell activation, but which are associated with inflammation in HIV patients.

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Decreased NK Cell FcRγ in HIV-1 Infected Individuals Receiving Combination Antiretroviral Therapy: a Cross Sectional Study

Cited by 18 publications

References 30 publications

Antibody Responses with Fc-Mediated Functions after Vaccination of HIV-Infected Subjects with Trivalent Influenza Vaccine

Antibody Responses with Fc-Mediated Functions after Vaccination of HIV-Infected Subjects with Trivalent Influenza Vaccine

Assessing immune aging in HIV-infected patients

Virologically Suppressed HIV Patients Show Activation of NK Cells and Persistent Innate Immune Activation

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