Activation of NK cells by HIV-specific ADCC antibodies

Madhavi, Vijaya; Navis, Marjon; Chung, Amy W.; Isitman, Gamze; Wren, Leia; Rose, Robert De; Kent, Stephen J.; Stratov, Ivan

doi:10.4161/hv.23446

Cited by 14 publications

(4 citation statements)

References 36 publications

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“…Nevertheless, the role of NK cell-mediated ADCC in the pathogenesis of HIV-1 remains controversial. A few studies have shown that NK cells in HIV-1-infected patients remain capable of mediating ADCC [76, 77], an activity that have been also reported to be specifically directed against Env, Pol, Vpu and Tat proteins [78, 79]. This NK cell recognition of HIV-1 via ADCC might also lead to viral escape in the presence of particular epitopes associated with protein variants [80].…”

Section: Nk Cells and Hiv-1 Pathogenesismentioning

confidence: 99%

Natural killer cells in HIV-1 infection and therapy

Mikulak

Oriolo

Zaghi

et al. 2017

Aids

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Natural killer (NK) cells are important effectors of innate immunity playing a key role in the eradication and clearance of viral infections. Over the recent years, several studies have shown that HIV-1 pathologically changes NK cell homeostasis and hampers their antiviral effector functions. Moreover, high levels of chronic HIV-1 viremia markedly impair those NK cell regulatory features that normally regulate the cross-talks between innate and adaptive immune responses. These pathogenic events take place early in the infection and are associated with a pathologic redistribution of NK cell subsets that includes the expansion of anergic CD56neg NK cells with an aberrant repertoire of activating and inhibitory receptors. Nevertheless, the presence of specific haplotypes for NK cell receptors as well as the engagement of NK cell antibody dependent cell cytotocity (ADCC) have been reported to control HIV-1 infection. This dichotomy can be extremely useful to both predict the clinical outcome of the infection and to develop alternative anti-viral pharmacological approaches. Indeed, the administration of antiretroviral therapy (ART) in HIV-1 infected patients restores NK cell phenotype and functions to normal levels. Thus, ART can help to develop NK cell-directed therapeutic strategies that include the use of broadly neutralizing antibodies and toll like receptor agonists. The present review discusses how our current knowledge of NK cell pathophysiology in HIV-1 infection is being translated both in experimental and clinical trials aimed at controlling the infection and disease.

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Section: Nk Cells and Hiv-1 Pathogenesismentioning

confidence: 99%

Natural killer cells in HIV-1 infection and therapy

Mikulak

Oriolo

Zaghi

et al. 2017

Aids

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“…The well-known Thai RV144 HIV vaccine trail showed 31% protection in preventing HIV acquisition with induction of robust HIV-specific ADCC responses [7–9]. In addition to NK cells, other types of circulating granulocytes, such as neutrophils, monocytes and macrophages, were also reported to mediate ADCC activity [10–14]. …”

Section: Introductionmentioning

confidence: 99%

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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“…Statistics within Results are presented as median (range) versus median (range), P value of statistical test. Previous research from our group has demonstrated that NK cells within whole blood can be stimulated to exhibit anti-HIV-1 Ab-dependent activation against autologous targets that bind and present HIV-1 proteins or peptides (17,26,27,34). These cellassociated antigens subsequently become bound by antiviral Abs that interact with the NK cell CD16 receptor, triggering degranulation and the release of cytokines.…”

Section: Subjectsmentioning

confidence: 99%

Slaying the Trojan Horse: Natural Killer Cells Exhibit Robust Anti-HIV-1 Antibody-Dependent Activation and Cytolysis against Allogeneic T Cells

Gooneratne

Richard

Lee

et al. 2015

J Virol

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Many attempts to design prophylactic human immunodeficiency virus type 1 (HIV-1A preventative vaccine is urgently needed to curb the growing human immunodeficiency virus type 1 (HIV-1) epidemic and reduce the global economic burden of supplying lifelong antiretroviral therapies. The induction of antibodies (Abs) capable of neutralizing a broad range of viral strains is a major goal of HIV-1 vaccine research. Such broadly neutralizing Abs (BnAbs) have been isolated from HIV-1-infected individuals, and passive transfer of BnAbs to nonhuman primates has proven sufficient to prevent infection upon challenge with cell-free chimeric simianhuman immunodeficiency viruses (SHIV) (1-3). Despite the potential of BnAbs to prevent HIV-1 infection, a vaccine capable of eliciting BnAbs in HIV-1-uninfected individuals has not yet been designed. The lack of appropriate immunogens and the extensive somatic hypermutation within the variable regions of BnAbs are major impediments to their induction via vaccination (4). This inability to elicit BnAbs through immunization has spurred research interest into the potential of nonneutralizing effector functions of Abs to provide protection against HIV-1.Interest in the potential of the nonneutralizing effector functions of Abs has also been stimulated by the recent phase III human RV144 vaccine trial in Thailand, which provided evidence that nonneutralizing Ab-associated effector functions may be involved in Ab-conferred protection against HIV-1 infection (5, 6). Indeed, correlates of immunity analyses revealed that, in the absence of broadly neutralizing Abs, both high levels of IgG Abs to the V1V2 regions of the HIV-1 Env and low levels of plasma an-

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Activation of NK cells by HIV-specific ADCC antibodies

Cited by 14 publications

References 36 publications

Natural killer cells in HIV-1 infection and therapy

Natural killer cells in HIV-1 infection and therapy

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

Slaying the Trojan Horse: Natural Killer Cells Exhibit Robust Anti-HIV-1 Antibody-Dependent Activation and Cytolysis against Allogeneic T Cells

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