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

Academic Article

Abstract

  • © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. 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 responders (ie, HIV-positive individuals with CD4 + T-cell counts of ≥500 cells/μL) 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.
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    Author List

  • Luo Z; Li Z; Martin L; Wan Z; Meissner EG; Espinosa E; Wu H; Yu X; Fu P; Julia Westerink MA
  • Start Page

  • 82
  • End Page

  • 91
  • Volume

  • 216
  • Issue

  • 1