Compromised NK Cell-Mediated Antibody-Dependent Cellular Cytotoxicity in Chronic SIV/SHIV Infection

He, Xuan; Li, Dan; Luo, Zhenwu; Liang, Hua; Peng, Hong; Zhao, Yangyang; Wang, Nidan; Liu, Donghua; Qin, Chuan; Wang, Qiang; Yan, Huimin; Shao, Yiming

doi:10.1371/journal.pone.0056309

Cited by 11 publications

(12 citation statements)

References 36 publications

(52 reference statements)

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“…Besides CD16, FcγRIIc (CD32) was also reported responsible for ADCC effect [20, 21]. In this study, the frequencies of CD16+ or CD32+ subsets in CD56+ T cells, CD3+ CD56+ NK cells and CD3+ CD56− T cells was identified and compared (Fig.…”

Section: Resultsmentioning

confidence: 81%

“…Routine blood tests, clinical biomedical tests, and CD4 +/CD8+ T cell counts were performed by local CDC. Peripheral blood mononuclear cells (PBMCs) were prepared from fresh EDTA anti-coagulated peripheral blood using Histopaque-1077 (Sigma, 10,771–500 ml) as described elsewhere [21] and were stored (5 × 10 6 cells per vial) in liquid nitrogen till use. Serum and EDTA anti-coagulated plasma were stored at −80 °C until use.…”

Section: Methodsmentioning

confidence: 99%

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Antibody-dependent CD56+ T cell responses are functionally impaired in long-term HIV-1 infection

et al. 2016

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BackgroundAntibody-dependent cellular cytotoxicity (ADCC), which mainly mediated by natural killer (NK) cells, may play a critical role in slowing human immunodeficiency virus type-1 (HIV-1) disease progression and protecting from HIV-1 infection. Besides classic NK cells, CD56+ T cells also have some NK cell-like properties, such as the large granular lymphocyte morphology and the capacity to destroy NK-sensitive target cells. However, little is known about the potentials of antibody-dependent CD56+ T cell responses and the association between antibody-dependent CD56+ T cell responses and HIV-1 disease progression.ResultsIn the present study, we showed evidences that, in addition to NK cells, CD56+ T cells could generate degranulation upon CD16 cross-linking. Ex vivo study showed that FcγRIII (CD16)-mediated CD56+ T cell responses were distinctly induced by IgG antibody-bound P815 cells. Comparatively, CD56− T cells and invariant NKT (CD3+ 6B11+) failed to induce antibody-dependent activation. Antibody-dependent CD56+ T cell responses were mainly ascribed to CD4/CD8 double negative subset and were functionally impaired in long-term HIV-1-infected former plasma donors, regardless of hepatitis C virus (HCV) coinfection status. Also, CD56+ T cell-mediated HIV-1-specific antibody-dependent responses were declined in men who have sex with men with HIV-1 infection over 3 years. Finally, we showed that matrix metalloprotease (MMP) inhibitor GM6001 could partially restored antibody-dependent CD56+ T cell responses of chronic HIV-1-infected subjects.ConclusionsOur results suggested that CD56+ T cells could mediate ADCC responses and the responses were impaired in chronic HIV-1 infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-016-0313-6) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 81%

Section: Methodsmentioning

confidence: 99%

Antibody-dependent CD56+ T cell responses are functionally impaired in long-term HIV-1 infection

et al. 2016

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“…The use of MMP inhibitors has been shown to result in both increased CD16 expression together with increased ADCC activity [185]. The changes seen in NK cells following SIV infection are similar to those described during chronic HIV infection [188], further supporting the macaque non-human primate model for vaccine development and correlates analysis.…”

Section: Complexity Of Immune Correlate Identificationmentioning

confidence: 83%

Fc Receptor-Mediated Immune Responses: New Tools But Increased Complexity in HIV Prevention

Vargas-Inchaustegui

Robert-Guroff²

2013

CHR

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The modest success of the RV144 HIV vaccine trial in Thailand and the ensuing suggestion that a Fc-receptor-mediated antibody activity might have played a role in the protection observed have intensified investigations on Fc-related immune responses. HIV neutralizing antibodies have been and continue to be the focal point of research into humoral immune protection. However, recent knowledge that their protective efficacy can be augmented by Fc-FcR interactions has increased the complexity of identifying immune correlates of protection. If anything, continued studies of both humoral and cellular immune mechanisms point to the lack of a single protective anti-HIV immune response. Here we focus on humoral immunity, analyzing the role played by Fc receptor-related responses and discussing how new knowledge of their interactions requires further investigation, but may also spur novel vaccination approaches. We initially address classical Fc-receptor mediated anti-viral mechanisms including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cell mediated viral inhibition (ADCVI), and antibody-dependent cellular phagocytosis (ADCP), as well as the effector cells that mediate these functions. Next, we summarize key aspects of FcR-Fc interactions that are important for potential control of HIV/SIV such as FcR polymorphisms and post-transcriptional modifications. Finally we discuss less commonly studied non-mechanistic anti-HIV immune functions: antibody avidity and envelope-specific B cell memory. Overall, a spectrum of immune responses, reflecting the immune system’s redundancy, will likely be needed to prevent HIV infection and/or disease progression. Aside from elicitation of critical immune mechanisms, a successful vaccine will need to induce mature B cell responses and long-lasting immune memory.

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“…The results on the role of NK cell function in HIV disease are conflicting [31, 33, 35, 42, 47, 59]. NK cells are shown to control HIV replication and kill HIV-infected cells through ADCC [60].…”

Section: Discussionmentioning

confidence: 99%

Increased Natural Killer Cell Activation in HIV-Infected Immunologic Non-Responders Correlates with CD4+ T Cell Recovery after Antiretroviral Therapy and Viral Suppression

Luo

Martin

et al. 2017

PLoS ONE

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The role of natural killer (NK) cell function in HIV disease especially in the setting of long-term antiretroviral therapy (ART) and viral suppression is not fully understood. In the current study, we have investigated NK cell activation in healthy controls and aviremic ART-treated HIV+ subjects with different degrees of immune restoration. We performed a cross sectional study in 12 healthy controls and 24 aviremic ART-treated HIV-infected subjects including 13 HIV+ subjects with CD4+ T cells above 500 cells/μL defined as “immunologic responders” and 11 HIV+ subjects with CD4+ T cells below 350 cells/μL defined as “immunologic non-responders”. We analyzed NK cell number, subset, and activation by expression of CD107a and NKG2D and co-expression of CD38 and HLA-DR. NK cell-mediated cytotoxicity against uninfected CD4+ T cells was tested in vitro. We found that NK cell absolute number, percentage of NK cells, and percentage of NK cell subsets were similar in the three study groups. The increased NK cell activation was found predominantly in CD56dimCD16+ subset of immunologic non-responders but not immunologic responders compared to healthy controls. The activation of NK cells was inversely correlated with the peripheral CD4+ T cell count in HIV+ subjects, even after controlling for chronic T cell activation, sex, and age, potential contributors for CD4+ T cell counts in HIV disease. Interestingly, NK cells from immunologic non-responders mediated cytotoxicity against uninfected CD4+ T cells ex vivo. NK cells may play a role in blunted CD4+ T cell recovery in ART-treated HIV disease.

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Compromised NK Cell-Mediated Antibody-Dependent Cellular Cytotoxicity in Chronic SIV/SHIV Infection

Cited by 11 publications

References 36 publications

Antibody-dependent CD56+ T cell responses are functionally impaired in long-term HIV-1 infection

Antibody-dependent CD56+ T cell responses are functionally impaired in long-term HIV-1 infection

Fc Receptor-Mediated Immune Responses: New Tools But Increased Complexity in HIV Prevention

Increased Natural Killer Cell Activation in HIV-Infected Immunologic Non-Responders Correlates with CD4+ T Cell Recovery after Antiretroviral Therapy and Viral Suppression

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