Antibody-Dependent Cellular Cytotoxicity against Primary HIV-Infected CD4+ T Cells Is Directly Associated with the Magnitude of Surface IgG Binding
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| Published in: | Journal of Virology Vol. 86; no. 16; pp. 8672 - 8680 |
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| Main Authors: | , , , , , , , , , , , , , , , |
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| Language: | English |
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01-08-2012
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| AbstractList | Antibody (Ab)-dependent cellular cytotoxicity (ADCC) is thought to potentially play a role in vaccine-induced protection from HIV-1. The characteristics of such antibodies remain incompletely understood. Furthermore, correlates between ADCC and HIV-1 immune status are not clearly defined. We screened the sera of 20 HIV-1-positive (HIV-1
+
) patients for ADCC. Normal human peripheral blood mononuclear cells were used to derive HIV-infected CD4
+
T cell targets and autologous, freshly isolated, natural killer (NK) cells in a novel assay that measures granzyme B (GrB) and HIV-1-infected CD4
+
T cell elimination (ICE) by flow cytometry. We observed that complex sera mediated greater levels of ADCC than anti-HIV-1 envelope glycoprotein (Env)-specific monoclonal antibodies and serum-mediated ADCC correlated with the amount of IgG and IgG1 bound to HIV-1-infected CD4
+
T cells. No correlation between ADCC and viral load, CD4
+
T cell count, or neutralization of HIV-1
SF162
or other primary viral isolates was detected. Sera pooled from clade B HIV-1
+
individuals exhibited breadth in killing targets infected with HIV-1 from clades A/E, B, and C. Taken together, these data suggest that the total amount of IgG bound to an HIV-1-infected cell is an important determinant of ADCC and that polyvalent antigen-specific Abs are required for a robust ADCC response. In addition, Abs elicited by a vaccine formulated with immunogens from a single clade may generate a protective ADCC response
in vivo
against a variety of HIV-1 species. Increased understanding of the parameters that dictate ADCC against HIV-1-infected cells will inform efforts to stimulate ADCC activity and improve its potency in vaccinees. Antibody (Ab)-dependent cellular cytotoxicity (ADCC) is thought to potentially play a role in vaccine-induced protection from HIV-1. The characteristics of such antibodies remain incompletely understood. Furthermore, correlates between ADCC and HIV-1 immune status are not clearly defined. We screened the sera of 20 HIV-1-positive (HIV-1(+)) patients for ADCC. Normal human peripheral blood mononuclear cells were used to derive HIV-infected CD4(+) T cell targets and autologous, freshly isolated, natural killer (NK) cells in a novel assay that measures granzyme B (GrB) and HIV-1-infected CD4(+) T cell elimination (ICE) by flow cytometry. We observed that complex sera mediated greater levels of ADCC than anti-HIV-1 envelope glycoprotein (Env)-specific monoclonal antibodies and serum-mediated ADCC correlated with the amount of IgG and IgG1 bound to HIV-1-infected CD4(+) T cells. No correlation between ADCC and viral load, CD4(+) T cell count, or neutralization of HIV-1(SF162) or other primary viral isolates was detected. Sera pooled from clade B HIV-1(+) individuals exhibited breadth in killing targets infected with HIV-1 from clades A/E, B, and C. Taken together, these data suggest that the total amount of IgG bound to an HIV-1-infected cell is an important determinant of ADCC and that polyvalent antigen-specific Abs are required for a robust ADCC response. In addition, Abs elicited by a vaccine formulated with immunogens from a single clade may generate a protective ADCC response in vivo against a variety of HIV-1 species. Increased understanding of the parameters that dictate ADCC against HIV-1-infected cells will inform efforts to stimulate ADCC activity and improve its potency in vaccinees. Article Usage Stats Services JVI Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue JVI About JVI Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy JVI RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0022-538X Online ISSN: 1098-5514 Copyright © 2014 by the American Society for Microbiology. For an alternate route to JVI .asm.org, visit: JVI |
| Author | Claire W. Hallahan Hing Wong Sung-Youl Ko Stephen A. Migueles Adjoa Smalls-Mantey Mark Connors Nicole Doria-Rose Rachel Klein Lijing You Christina Ochsenbauer John R. Mascola Gary J. Nabel John C. Kappes Johannes Scheid Andy Patamawenu Bai Liu |
| Author_xml | – sequence: 1 givenname: Adjoa surname: SMALLS-MANTEY fullname: SMALLS-MANTEY, Adjoa organization: HIV-Specific Immunity Section, Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Maryland, United States – sequence: 2 givenname: Nicole surname: DORIA-ROSE fullname: DORIA-ROSE, Nicole organization: HIV-Specific Immunity Section, Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Maryland, United States – sequence: 3 givenname: Johannes surname: SCHEID fullname: SCHEID, Johannes organization: Laboratory of Molecular Immunology, Rockefeller University, New York, New York, United States – sequence: 4 givenname: John C surname: KAPPES fullname: KAPPES, John C organization: Departments of Medicine, University of Alabama, Birmingham, Alabama, United States – sequence: 5 givenname: Christina surname: OCHSENBAUER fullname: OCHSENBAUER, Christina organization: Departments of Medicine, University of Alabama, Birmingham, Alabama, United States – sequence: 6 givenname: Gary J surname: NABEL fullname: NABEL, Gary J organization: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States – sequence: 7 givenname: John R surname: MASCOLA fullname: MASCOLA, John R organization: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States – sequence: 8 givenname: Mark surname: CONNORS fullname: CONNORS, Mark organization: HIV-Specific Immunity Section, Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Maryland, United States – sequence: 9 givenname: Rachel surname: KLEIN fullname: KLEIN, Rachel organization: HIV-Specific Immunity Section, Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Maryland, United States – sequence: 10 givenname: Andy surname: PATAMAWENU fullname: PATAMAWENU, Andy organization: HIV-Specific Immunity Section, Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Maryland, United States – sequence: 11 givenname: Stephen A surname: MIGUELES fullname: MIGUELES, Stephen A organization: HIV-Specific Immunity Section, Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Maryland, United States – sequence: 12 givenname: Sung-Youl surname: KO fullname: KO, Sung-Youl organization: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States – sequence: 13 givenname: Claire W surname: HALLAHAN fullname: HALLAHAN, Claire W organization: Biostatistics Research Branch, NIAID, NIH, Bethesda, Maryland, United States – sequence: 14 givenname: Hing surname: WONG fullname: WONG, Hing organization: Altor BioScience, Miramar, Florida, United States – sequence: 15 surname: BAI LIU fullname: BAI LIU organization: Altor BioScience, Miramar, Florida, United States – sequence: 16 surname: LIJING YOU fullname: LIJING YOU organization: Altor BioScience, Miramar, Florida, United States |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26224402$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/22674985$$D View this record in MEDLINE/PubMed |
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| Copyright | 2015 INIST-CNRS Copyright © 2012, American Society for Microbiology. All Rights Reserved. 2012 American Society for Microbiology |
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Mendeley... Antibody (Ab)-dependent cellular cytotoxicity (ADCC) is thought to potentially play a role in vaccine-induced protection from HIV-1. The characteristics of... |
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| SubjectTerms | Antibodies, Neutralizing - blood Biological and medical sciences CD4 Lymphocyte Count CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - virology Cell Survival Cytotoxicity, Immunologic Flow Cytometry Fundamental and applied biological sciences. Psychology HIV Antibodies - blood HIV Antibodies - immunology HIV Infections - immunology HIV-1 - immunology Humans Immunoglobulin G - immunology Microbiology Miscellaneous Pathogenesis and Immunity Viral Load Virology |
| Title | Antibody-Dependent Cellular Cytotoxicity against Primary HIV-Infected CD4+ T Cells Is Directly Associated with the Magnitude of Surface IgG Binding |
| URI | http://jvi.asm.org/content/86/16/8672.abstract https://www.ncbi.nlm.nih.gov/pubmed/22674985 https://search.proquest.com/docview/1030348999 https://pubmed.ncbi.nlm.nih.gov/PMC3421757 |
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