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Increased homeostatic cytokines and stability of HIV-infected memory CD4 T-cells identify individuals with suboptimal CD4 T-cell recovery on-ART
Clinical outcomes are inferior for individuals with HIV having suboptimal CD4 T-cell recovery during antiretroviral therapy (ART). We investigated if the levels of infection and the response to homeostatic cytokines of CD4 T-cell subsets contributed to divergent CD4 T-cell recovery and HIV reservoir...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397407/ https://www.ncbi.nlm.nih.gov/pubmed/34449812 http://dx.doi.org/10.1371/journal.ppat.1009825 |
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author | Pino, Maria Pereira Ribeiro, Susan Pagliuzza, Amélie Ghneim, Khader Khan, Anum Ryan, Emily Harper, Justin L. King, Colin T. Welbourn, Sarah Micci, Luca Aldrete, Sol Delman, Keith A. Stuart, Theron Lowe, Michael Brenchley, Jason M. Derdeyn, Cynthia A. Easley, Kirk Sekaly, Rafick P. Chomont, Nicolas Paiardini, Mirko Marconi, Vincent C. |
author_facet | Pino, Maria Pereira Ribeiro, Susan Pagliuzza, Amélie Ghneim, Khader Khan, Anum Ryan, Emily Harper, Justin L. King, Colin T. Welbourn, Sarah Micci, Luca Aldrete, Sol Delman, Keith A. Stuart, Theron Lowe, Michael Brenchley, Jason M. Derdeyn, Cynthia A. Easley, Kirk Sekaly, Rafick P. Chomont, Nicolas Paiardini, Mirko Marconi, Vincent C. |
author_sort | Pino, Maria |
collection | PubMed |
description | Clinical outcomes are inferior for individuals with HIV having suboptimal CD4 T-cell recovery during antiretroviral therapy (ART). We investigated if the levels of infection and the response to homeostatic cytokines of CD4 T-cell subsets contributed to divergent CD4 T-cell recovery and HIV reservoir during ART by studying virologically-suppressed immunologic responders (IR, achieving a CD4 cell count >500 cells/μL on or before two years after ART initiation), and virologically-suppressed suboptimal responders (ISR, did not achieve a CD4 cell count >500 cells/μL in the first two years after ART initiation). Compared to IR, ISR demonstrated higher levels of HIV-DNA in naïve, central (CM), transitional (TM), and effector (EM) memory CD4 T-cells in blood, both pre- and on-ART, and specifically in CM CD4 T-cells in LN on-ART. Furthermore, ISR had higher pre-ART plasma levels of IL-7 and IL-15, cytokines regulating T-cell homeostasis. Notably, pre-ART PD-1 and TIGIT expression levels were higher in blood CM and TM CD4 T-cells for ISR; this was associated with a significantly lower fold-changes in HIV-DNA levels between pre- and on-ART time points exclusively on CM and TM T-cell subsets, but not naïve or EM T-cells. Finally, the frequency of CM CD4 T-cells expressing PD-1 or TIGIT pre-ART as well as plasma levels of IL-7 and IL-15 predicted HIV-DNA content on-ART. Our results establish the association between infection, T-cell homeostasis, and expression of PD-1 and TIGIT in long-lived CD4 T-cell subsets prior to ART with CD4 T-cell recovery and HIV persistence on-ART. |
format | Online Article Text |
id | pubmed-8397407 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-83974072021-08-28 Increased homeostatic cytokines and stability of HIV-infected memory CD4 T-cells identify individuals with suboptimal CD4 T-cell recovery on-ART Pino, Maria Pereira Ribeiro, Susan Pagliuzza, Amélie Ghneim, Khader Khan, Anum Ryan, Emily Harper, Justin L. King, Colin T. Welbourn, Sarah Micci, Luca Aldrete, Sol Delman, Keith A. Stuart, Theron Lowe, Michael Brenchley, Jason M. Derdeyn, Cynthia A. Easley, Kirk Sekaly, Rafick P. Chomont, Nicolas Paiardini, Mirko Marconi, Vincent C. PLoS Pathog Research Article Clinical outcomes are inferior for individuals with HIV having suboptimal CD4 T-cell recovery during antiretroviral therapy (ART). We investigated if the levels of infection and the response to homeostatic cytokines of CD4 T-cell subsets contributed to divergent CD4 T-cell recovery and HIV reservoir during ART by studying virologically-suppressed immunologic responders (IR, achieving a CD4 cell count >500 cells/μL on or before two years after ART initiation), and virologically-suppressed suboptimal responders (ISR, did not achieve a CD4 cell count >500 cells/μL in the first two years after ART initiation). Compared to IR, ISR demonstrated higher levels of HIV-DNA in naïve, central (CM), transitional (TM), and effector (EM) memory CD4 T-cells in blood, both pre- and on-ART, and specifically in CM CD4 T-cells in LN on-ART. Furthermore, ISR had higher pre-ART plasma levels of IL-7 and IL-15, cytokines regulating T-cell homeostasis. Notably, pre-ART PD-1 and TIGIT expression levels were higher in blood CM and TM CD4 T-cells for ISR; this was associated with a significantly lower fold-changes in HIV-DNA levels between pre- and on-ART time points exclusively on CM and TM T-cell subsets, but not naïve or EM T-cells. Finally, the frequency of CM CD4 T-cells expressing PD-1 or TIGIT pre-ART as well as plasma levels of IL-7 and IL-15 predicted HIV-DNA content on-ART. Our results establish the association between infection, T-cell homeostasis, and expression of PD-1 and TIGIT in long-lived CD4 T-cell subsets prior to ART with CD4 T-cell recovery and HIV persistence on-ART. Public Library of Science 2021-08-27 /pmc/articles/PMC8397407/ /pubmed/34449812 http://dx.doi.org/10.1371/journal.ppat.1009825 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article Pino, Maria Pereira Ribeiro, Susan Pagliuzza, Amélie Ghneim, Khader Khan, Anum Ryan, Emily Harper, Justin L. King, Colin T. Welbourn, Sarah Micci, Luca Aldrete, Sol Delman, Keith A. Stuart, Theron Lowe, Michael Brenchley, Jason M. Derdeyn, Cynthia A. Easley, Kirk Sekaly, Rafick P. Chomont, Nicolas Paiardini, Mirko Marconi, Vincent C. Increased homeostatic cytokines and stability of HIV-infected memory CD4 T-cells identify individuals with suboptimal CD4 T-cell recovery on-ART |
title | Increased homeostatic cytokines and stability of HIV-infected memory CD4 T-cells identify individuals with suboptimal CD4 T-cell recovery on-ART |
title_full | Increased homeostatic cytokines and stability of HIV-infected memory CD4 T-cells identify individuals with suboptimal CD4 T-cell recovery on-ART |
title_fullStr | Increased homeostatic cytokines and stability of HIV-infected memory CD4 T-cells identify individuals with suboptimal CD4 T-cell recovery on-ART |
title_full_unstemmed | Increased homeostatic cytokines and stability of HIV-infected memory CD4 T-cells identify individuals with suboptimal CD4 T-cell recovery on-ART |
title_short | Increased homeostatic cytokines and stability of HIV-infected memory CD4 T-cells identify individuals with suboptimal CD4 T-cell recovery on-ART |
title_sort | increased homeostatic cytokines and stability of hiv-infected memory cd4 t-cells identify individuals with suboptimal cd4 t-cell recovery on-art |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397407/ https://www.ncbi.nlm.nih.gov/pubmed/34449812 http://dx.doi.org/10.1371/journal.ppat.1009825 |
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