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

Zhenwu Luo, Zhen Li, Lisa Martin, Zhuang Wan, Eric G. Meissner, Enrique Espinosa, Hao Wu, Xiaocong Yu, Pingfu Fu, Maria Anna Julia Westerink, J. Michael Kilby, Jennifer Wu, Lei Huang, Sonya L. Heath, Zihai Li, Wei Jiang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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/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.

Original languageEnglish (US)
Pages (from-to)82-91
Number of pages10
JournalJournal of Infectious Diseases
Volume216
Issue number1
DOIs
StatePublished - Jul 1 2017

Keywords

  • B cells
  • HIV
  • antibody responses
  • autoreactive anti-CD4 antibodies

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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