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

Autor:	Luo Z; Department of Microbiology and Immunology., Li Z; Department of Microbiology and Immunology.; Beijing You'an Hospital, Capital Medical University., Martin L; Divison of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston., Wan Z; Department of Microbiology and Immunology., Meissner EG; Department of Microbiology and Immunology.; Divison of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston., Espinosa E; Department of Integrative in Immunology, National Institute for Respiratory Diseases, Mexico City, Mexico., Wu H; Beijing You'an Hospital, Capital Medical University., Yu X; Department of Medicine, University of Massachusetts Medical School, Worcester., Fu P; Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio., Julia Westerink MA; Divison of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston., Kilby JM; Divison of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston., Wu J; Department of Microbiology and Immunology., Huang L; Treatment and Research Center for Infectious Diseases, 302nd Hospital of the PLA, Beijing, China., Heath SL; Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham., Li Z; Department of Microbiology and Immunology., Jiang W; Department of Microbiology and Immunology.; Divison of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2017 Jul 01; Vol. 216 (1), pp. 82-91.
DOI:	10.1093/infdis/jix223
Abstrakt:	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. (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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