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Combined Effects of HLA-B*57/5801 Elite Suppressor CD8+ T Cells and NK Cells on HIV-1 Replication

Elite controllers or suppressors (ES) are HIV-1 infected individuals who maintain undetectable viral loads without anti-retroviral therapy. The HLA-B*57 allele is overrepresented in ES suggesting a role for HIV-specific CD8+ T cells in immune control. Natural killer (NK) cells also play a role in co...

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Autores principales: May, Megan E., Pohlmeyer, Christopher W., Kwaa, Abena K., Mankowski, Madeleine C., Bailey, Justin R., Blankson, Joel N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098910/
https://www.ncbi.nlm.nih.gov/pubmed/32266164
http://dx.doi.org/10.3389/fcimb.2020.00113
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author May, Megan E.
Pohlmeyer, Christopher W.
Kwaa, Abena K.
Mankowski, Madeleine C.
Bailey, Justin R.
Blankson, Joel N.
author_facet May, Megan E.
Pohlmeyer, Christopher W.
Kwaa, Abena K.
Mankowski, Madeleine C.
Bailey, Justin R.
Blankson, Joel N.
author_sort May, Megan E.
collection PubMed
description Elite controllers or suppressors (ES) are HIV-1 infected individuals who maintain undetectable viral loads without anti-retroviral therapy. The HLA-B*57 allele is overrepresented in ES suggesting a role for HIV-specific CD8+ T cells in immune control. Natural killer (NK) cells also play a role in controlling viral replication, and genetic studies demonstrate that specific combinations of killer cell immunoglobulin-like receptor (KIR) alleles and HLA subtypes including HLA-B*57 correlate with delayed progression to AIDS. While prior studies have shown that both HIV-specific CD8+ T cells and NK cells can inhibit viral replication in vitro, the interaction between these two effector cells has not been studied. We performed in vitro suppression assays using CD8+ T cells and NK cells from HLA-B*57 ES either alone or in combination with each other. We found no evidence of antagonism or synergy between the CD8+ T cells and NK cells, suggesting that they have independent mechanisms of inhibition in vitro. Our data has implications for combined immunotherapy with CD8+ T cells and NK cells in HIV cure strategies.
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spelling pubmed-70989102020-04-07 Combined Effects of HLA-B*57/5801 Elite Suppressor CD8+ T Cells and NK Cells on HIV-1 Replication May, Megan E. Pohlmeyer, Christopher W. Kwaa, Abena K. Mankowski, Madeleine C. Bailey, Justin R. Blankson, Joel N. Front Cell Infect Microbiol Cellular and Infection Microbiology Elite controllers or suppressors (ES) are HIV-1 infected individuals who maintain undetectable viral loads without anti-retroviral therapy. The HLA-B*57 allele is overrepresented in ES suggesting a role for HIV-specific CD8+ T cells in immune control. Natural killer (NK) cells also play a role in controlling viral replication, and genetic studies demonstrate that specific combinations of killer cell immunoglobulin-like receptor (KIR) alleles and HLA subtypes including HLA-B*57 correlate with delayed progression to AIDS. While prior studies have shown that both HIV-specific CD8+ T cells and NK cells can inhibit viral replication in vitro, the interaction between these two effector cells has not been studied. We performed in vitro suppression assays using CD8+ T cells and NK cells from HLA-B*57 ES either alone or in combination with each other. We found no evidence of antagonism or synergy between the CD8+ T cells and NK cells, suggesting that they have independent mechanisms of inhibition in vitro. Our data has implications for combined immunotherapy with CD8+ T cells and NK cells in HIV cure strategies. Frontiers Media S.A. 2020-03-20 /pmc/articles/PMC7098910/ /pubmed/32266164 http://dx.doi.org/10.3389/fcimb.2020.00113 Text en Copyright © 2020 May, Pohlmeyer, Kwaa, Mankowski, Bailey and Blankson. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
May, Megan E.
Pohlmeyer, Christopher W.
Kwaa, Abena K.
Mankowski, Madeleine C.
Bailey, Justin R.
Blankson, Joel N.
Combined Effects of HLA-B*57/5801 Elite Suppressor CD8+ T Cells and NK Cells on HIV-1 Replication
title Combined Effects of HLA-B*57/5801 Elite Suppressor CD8+ T Cells and NK Cells on HIV-1 Replication
title_full Combined Effects of HLA-B*57/5801 Elite Suppressor CD8+ T Cells and NK Cells on HIV-1 Replication
title_fullStr Combined Effects of HLA-B*57/5801 Elite Suppressor CD8+ T Cells and NK Cells on HIV-1 Replication
title_full_unstemmed Combined Effects of HLA-B*57/5801 Elite Suppressor CD8+ T Cells and NK Cells on HIV-1 Replication
title_short Combined Effects of HLA-B*57/5801 Elite Suppressor CD8+ T Cells and NK Cells on HIV-1 Replication
title_sort combined effects of hla-b*57/5801 elite suppressor cd8+ t cells and nk cells on hiv-1 replication
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098910/
https://www.ncbi.nlm.nih.gov/pubmed/32266164
http://dx.doi.org/10.3389/fcimb.2020.00113
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