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Pathological Role of Anti-CD4 Antibodies in HIV-Infected Immunologic Nonresponders Receiving Virus-Suppressive Antiretroviral Therapy.


ABSTRACT: Increased mortality and morbidity occur among human immunodeficiency virus (HIV)-infected patients in whom CD4+ T-cell counts do not increase despite viral suppression with antiretroviral therapy (ART). Here we identified an underlying mechanism. Significantly elevated plasma levels of anti-CD4 immunoglobulin G (IgG) were found in HIV-positive immunologic nonresponders (ie, HIV-positive individuals with CD4+ T-cell counts of ?350 cells/?L), compared with levels in HIV-positive immunologic responders (ie, HIV-positive individuals with CD4+ T-cell counts of ?500 cells/?L) and healthy controls. Higher plasma level of anti-CD4 IgG correlated with blunted CD4+ T-cell recovery. Furthermore, purified anti-CD4 IgG from HIV-positive immunologic nonresponders induced natural killer (NK) cell-dependent CD4+ T-cell cytolysis and apoptosis through antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. We also found that anti-CD4 IgG-mediated ADCC exerts greater apoptosis of naive CD4+ T cells relative to memory CD4+ T cells. Consistently, increased frequencies of CD107a+ NK cells and profound decreases of naive CD4+ T cells were observed in immunologic nonresponders as compared to responders and healthy controls ex vivo. These data indicate that autoreactive anti-CD4 IgG may play an important role in blunted CD4+ T-cell reconstitution despite effective ART.

SUBMITTER: Luo Z 

PROVIDER: S-EPMC5853506 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Pathological Role of Anti-CD4 Antibodies in HIV-Infected Immunologic Nonresponders Receiving Virus-Suppressive Antiretroviral Therapy.

Luo Zhenwu Z   Li Zhen Z   Martin Lisa L   Wan Zhuang Z   Meissner Eric G EG   Espinosa Enrique E   Wu Hao H   Yu Xiaocong X   Fu Pingfu P   Julia Westerink Maria Anna MA   Kilby J Michael JM   Wu Jennifer J   Huang Lei L   Heath Sonya L SL   Li Zihai Z   Jiang Wei W  

The Journal of infectious diseases 20170701 1


Increased mortality and morbidity occur among human immunodeficiency virus (HIV)-infected patients in whom CD4+ T-cell counts do not increase despite viral suppression with antiretroviral therapy (ART). Here we identified an underlying mechanism. Significantly elevated plasma levels of anti-CD4 immunoglobulin G (IgG) were found in HIV-positive immunologic nonresponders (ie, HIV-positive individuals with CD4+ T-cell counts of ≤350 cells/μL), compared with levels in HIV-positive immunologic respon  ...[more]

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