HIV-Specific ADCC Improves After Antiretroviral Therapy and Correlates With Normalization of the NK Cell Phenotype

Jensen, Sanne; Hartling, Hans J.; Tingstedt, Jeanette Linnea; Larsen, Tine; Nielsen, Susanne Dam; Pedersen, Court; Fomsgaard, Anders; Karlsson, Ingrid

doi:10.1097/qai.0000000000000429

Cited by 15 publications

(15 citation statements)

References 31 publications

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“…It is possible that a shorter duration of ART would be sufficient to accomplish the same improvement in the CD8 + T cell phenotype. For example, we have previously shown that for NK cells, six months of ART is sufficient for a significant restoration of phenotype [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Initiation of Antiretroviral Therapy (ART) at Different Stages of HIV-1 Disease Is Not Associated with the Proportion of Exhausted CD8+ T Cells

et al. 2015

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CD8+ T cell-restricted immunity is important in the control of HIV-1 infection, but continued immune activation results in CD8+ T cell dysfunction. Early initiation of antiretroviral treatment (ART) and the duration of ART have been associated with immune reconstitution. Here, we evaluated whether restoration of CD8+ T cell function in HIV-1-infected individuals was dependent on early initiation of ART. HIV-specific CD107a, IFNγ, IL-2, TNFα and MIP-1β expression by CD8+ T cells and the frequency of CD8+ T cells expressing PD-1, 2B4 and CD160 were measured by flow cytometry. The frequency of CD8+ T cells expressing the inhibitory markers PD-1, 2B4 and CD160 was lower in ART-treated individuals compared with ART-naïve individuals and similar to the frequency in HIV-uninfected controls. The expression of the three markers was similarly independent of when therapy was initiated. Individuals treated before seroconversion displayed an HIV-specific CD8+ T cell response that included all five functional markers; this was not observed in individuals treated after seroconversion or in ART-naïve individuals. In summary, ART appears to restore the total CD8+ T cell population to a less exhausted phenotype, independent of the time point of initiation. However, to preserve multifunctional, HIV-1-specific CD8+ T cells, ART might have to be initiated before seroconversion.

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Section: Discussionmentioning

confidence: 99%

Initiation of Antiretroviral Therapy (ART) at Different Stages of HIV-1 Disease Is Not Associated with the Proportion of Exhausted CD8+ T Cells

et al. 2015

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“…Indeed, the earlier ART is administered to HIV-1-infected patients, the more pronounced is the recovery of NK cell-mediated ADCC. This immune response reaches its highest peak if the antiviral treatment starts prior to sero-conversion and/or when the CD4 + T cell counts is above 350 cells/μl [120–122]. Importantly, the exposure of NK cells to IL-10 has been shown to reproduce an aberrant repertoire of NKRs that is similar to that observed during the course of HIV-1 infection.…”

Section: Nk Cells and Antiretroviral Therapymentioning

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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“…ADCC activity was detected using PanToxiLux (On-coImmunin, Gaithersburg, MD) according to the previously described ADCC-GranToxiLux procedure. 43,44 Env-coated CEM.NKR CCR5 cells 45 were used as target cells and coated 90 min at 4°C with recombinant Env. Env-coated target cells have previously been demonstrated to be equally effective in the ADCC assay as infected target cells, 44 which we confirmed in a separate experiment (data not shown).…”

Section: Adcc Assaymentioning

confidence: 99%

Neutralizing Antibody Response and Antibody-Dependent Cellular Cytotoxicity in HIV-1–Infected Individuals from Guinea-Bissau and Denmark

Borggren

Jensen

Heyndrickx

et al. 2016

AIDS Research and Human Retroviruses

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The development of therapeutic and prophylactic HIV vaccines for African countries is urgently needed, but the question of what immunogens to use needs to be answered. One approach is to include HIV envelope immunogens derived from HIV-positive individuals from a geographically concentrated epidemic with more limited viral genetic diversity for a region-based vaccine. To address if there is a basis for a regional selected antibody vaccine, we have screened two regionally separate cohorts from Guinea-Bissau and Denmark for neutralizing antibody activity and antibody-dependent cellular cytotoxicity (ADCC) against local and nonlocal circulating HIV-1 strains. The neutralizing activity did not demonstrate higher potential against local circulating strains according to geography and subtype determination, but the plasma from Danish individuals demonstrated significantly higher inhibitory activity than that from Guinea-Bissau individuals against both local and nonlocal virus strains. Interestingly, an opposite pattern was observed with ADCC activity, where Guinea-Bissau individual plasma demonstrated higher activity than Danish plasma and was specifically against the local circulating subtype. Thus, on basis of samples from these two cohorts, no local-specific neutralizing activity was detected, but a local ADCC response was identified in the Guinea-Bissau samples, suggesting potential use of regional immunogens for an ADCC-inducing vaccine.

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HIV-Specific ADCC Improves After Antiretroviral Therapy and Correlates With Normalization of the NK Cell Phenotype

Abstract: HAART improves the ability of NK cells to mediate ADCC after 6 months. This improvement does not correlate with general immune restoration, as measured by CD4 T-cell counts, but rather to a decrease in the frequency of NK cells expressing CCR7 and CD27.

Cited by 15 publications

References 31 publications

Initiation of Antiretroviral Therapy (ART) at Different Stages of HIV-1 Disease Is Not Associated with the Proportion of Exhausted CD8+ T Cells

Initiation of Antiretroviral Therapy (ART) at Different Stages of HIV-1 Disease Is Not Associated with the Proportion of Exhausted CD8+ T Cells

Natural killer cells in HIV-1 infection and therapy

Neutralizing Antibody Response and Antibody-Dependent Cellular Cytotoxicity in HIV-1–Infected Individuals from Guinea-Bissau and Denmark

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