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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
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.
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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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