Antibody-Dependent Cellular Cytotoxicity against Primary HIV-Infected CD4<sup>+</sup>T Cells Is Directly Associated with the Magnitude of Surface IgG Binding

Smalls-Mantey, Adjoa; Doria‐Rose, Nicole A.; Klein, Rachel M.; Patamawenu, Andy; Migueles, Stephen A.; Ko, Sung-Youl; Hallahan, Claire W.; Wong, Hing C.; Liu, Bai; You, Lijing; Scheid, Johannes F.; Kappes, John C.; Ochsenbauer, Christina; Nabel, Gary J.; Mascola, John R.; Connors, Mark

doi:10.1128/jvi.00287-12

Cited by 93 publications

(89 citation statements)

References 55 publications

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“…These results suggest that HIV-1 gp120-specific antibodies in the serum of infected individuals in this study had cross-reactive ADCC antibodies at asymptomatic stages of infection. These data are consistent with a previous report of cross-clade ADCC activity in HIV-infected individuals 34 and extend this observation, showing that sex does not have an effect on cross-clade reactivity.…”

Section: Cd4supporting

confidence: 83%

Comparison of Antibodies That Mediate HIV Type 1 gp120 Antibody-Dependent Cell-Mediated Cytotoxicity in Asymptomatic HIV Type 1-Positive Men and Women

Mata

Iwema

Dell

et al. 2014

AIDS Research and Human Retroviruses

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Recent studies suggest that HIV-specific antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies contribute to protective immunity against HIV. An important characteristic of future HIV vaccines will, therefore, be the ability to stimulate production of these antibodies in both men and women. Early studies suggest that men may have a better ADCC antibody response against HIV than women. Our objective was to determine whether men and women differ with respect to their ADCC response to HIV-1 gp120. HIV-positive, asymptomatic untreated men and women were matched for race, age, CD4+ T cell number, HIV-1 viral load, and treatment and HIV-1 gp120 ADCC antibody titers were compared. A standard 51 Cr-release assay was used to determine HIV-1 gp120 ADCC antibody titers in HIV-1-seropositive individuals from the Multicenter AIDS Cohort Study (MACS; n = 32) and the Women's Interagency HIV Study (WIHS; n = 32). Both sexes had high ADCC titers against HIV-1 gp120: 34.4% (n = 11) and 40.6% (n = 13) of men and women, respectively, had titers of 10,000; 62.5% (n = 20) and 56.3% (n = 18) had titers of 100,000. Groups did not differ in percent specific release (% SR), lytic units (LU), correlations of titer to viral load, or titer to CD4 + T cells in men or women. Both groups also had similar cross-clade ADCC antibody responses ( p > 0.5 for % SR and LU). Comparable groups of asymptomatic HIV-1-infected men and women had comparable HIV-1 gp120 ADCC antibodies. Both sexes had significant cross-clade reactivity. Differences between men and women may become evident as disease progresses; this should be evaluated at later stages of HIV-1 infection.

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Section: Cd4supporting

confidence: 83%

Comparison of Antibodies That Mediate HIV Type 1 gp120 Antibody-Dependent Cell-Mediated Cytotoxicity in Asymptomatic HIV Type 1-Positive Men and Women

Mata

Iwema

Dell

et al. 2014

AIDS Research and Human Retroviruses

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“…We now show that activation-induced MMP production decreases NKp46 expression on NK cells. We note that it will be useful to corroborate our findings of NKp46 downregulation on NK cells activated through CD16 with studies analyzing NKp46 expression on NK cells activated by Ab-coated HIV-infected cells (40)(41)(42). However, the currently presented observation raises several questions about the role of anti-HIV ADCC, and antiviral NK cell responses in general, in slowing the progression of chronic HIV infection toward AIDS.…”

Section: Discussionsupporting

confidence: 54%

Anti-HIV Antibody–Dependent Activation of NK Cells Impairs NKp46 Expression

Parsons

Tang

Jegaskanda

et al. 2014

The Journal of Immunology

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There is much interest in the potential of Ab-dependent cellular cytotoxicity (ADCC) to slow disease progression following HIV infection. Despite several studies demonstrating a positive association between ADCC and slower disease progression, it is possible that continued stimulation of NK cells by ADCC during chronic HIV infection could render these cells dysfunctional. Indeed, activation of NK cells by ADCC results in matrix metalloproteinase–induced reductions in CD16 expression and activation refractory periods. In addition, ex vivo analyses of NK cells from HIV-infected individuals revealed other alterations in phenotype, such as decreased expression of the activating NKp46 receptor that is essential for NK-mediated antitumor responses and immunity from infection. Because NKp46 shares a signaling pathway with CD16, we hypothesized that activation-induced downregulation of both receptors could be controlled by a common mechanism. We found that activation of NK cells by anti-HIV or anti-CD16 Abs resulted in NKp46 downregulation. The addition of a matrix metalloproteinase inhibitor attenuated NKp46 downregulation following NK cell activation by anti-HIV Abs. Consequently, these results suggest that continued stimulation through CD16 has the potential to impair natural cytotoxicity via attenuation of NKp46-dependent signals.

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“…In their study, the one strain-specific anti-HA head Ab (PY102) investigated was inefficient at mediating FcgR binding and ADCC activity; however, more Abs to the globular head of HA need to be tested before clear conclusions can be drawn. Further, a polyclonal anti-HA ADCC response may provide greater ligation of CD16, as seen for HIV ADCC (54). Clearly, a larger subset of anti-HA head Abs needs to be tested to determine their overall potential to mediate ADCC.…”

Section: In Vivo Protection From Influenza Infection By Adcc-mediatinmentioning

confidence: 99%

Influenza-Specific Antibody-Dependent Cellular Cytotoxicity: Toward a Universal Influenza Vaccine

Jegaskanda

Reading

Kent

2014

The Journal of Immunology

116

137

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There is an urgent need for universal influenza vaccines that can control emerging pandemic influenza virus threats without the need to generate new vaccines for each strain. Neutralizing Abs to the influenza virus hemagglutinin glycoprotein are effective at controlling influenza infection but generally target highly variable regions. Abs that can mediate other functions, such as killing influenza-infected cells and activating innate immune responses (termed “Ab-dependent cellular cytotoxicity [ADCC]-mediating Abs”), may assist in protective immunity to influenza. ADCC-mediating Abs can target more conserved regions of influenza virus proteins and recognize a broader array of influenza strains. We review recent research on influenza-specific ADCC Abs and their potential role in improved influenza-vaccination strategies.

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Antibody-Dependent Cellular Cytotoxicity against Primary HIV-Infected CD4⁺T Cells Is Directly Associated with the Magnitude of Surface IgG Binding

Cited by 93 publications

References 55 publications

Comparison of Antibodies That Mediate HIV Type 1 gp120 Antibody-Dependent Cell-Mediated Cytotoxicity in Asymptomatic HIV Type 1-Positive Men and Women

Comparison of Antibodies That Mediate HIV Type 1 gp120 Antibody-Dependent Cell-Mediated Cytotoxicity in Asymptomatic HIV Type 1-Positive Men and Women

Anti-HIV Antibody–Dependent Activation of NK Cells Impairs NKp46 Expression

Influenza-Specific Antibody-Dependent Cellular Cytotoxicity: Toward a Universal Influenza Vaccine

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Antibody-Dependent Cellular Cytotoxicity against Primary HIV-Infected CD4+T Cells Is Directly Associated with the Magnitude of Surface IgG Binding

Cited by 93 publications

References 55 publications

Comparison of Antibodies That Mediate HIV Type 1 gp120 Antibody-Dependent Cell-Mediated Cytotoxicity in Asymptomatic HIV Type 1-Positive Men and Women

Comparison of Antibodies That Mediate HIV Type 1 gp120 Antibody-Dependent Cell-Mediated Cytotoxicity in Asymptomatic HIV Type 1-Positive Men and Women

Anti-HIV Antibody–Dependent Activation of NK Cells Impairs NKp46 Expression

Influenza-Specific Antibody-Dependent Cellular Cytotoxicity: Toward a Universal Influenza Vaccine

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Product

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Antibody-Dependent Cellular Cytotoxicity against Primary HIV-Infected CD4⁺T Cells Is Directly Associated with the Magnitude of Surface IgG Binding