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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2021
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oai:doaj.org-article:067e37f438b34fd7827433be61b176ba2021-12-02T20:00:21ZIncreased homeostatic cytokines and stability of HIV-infected memory CD4 T-cells identify individuals with suboptimal CD4 T-cell recovery on-ART.1553-73661553-737410.1371/journal.ppat.1009825https://doaj.org/article/067e37f438b34fd7827433be61b176ba2021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009825https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Clinical 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.Maria PinoSusan Pereira RibeiroAmélie PagliuzzaKhader GhneimAnum KhanEmily RyanJustin L HarperColin T KingSarah WelbournLuca MicciSol AldreteKeith A DelmanTheron StuartMichael LoweJason M BrenchleyCynthia A DerdeynKirk EasleyRafick P SekalyNicolas ChomontMirko PaiardiniVincent C MarconiPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 8, p e1009825 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Maria Pino Susan Pereira Ribeiro Amélie Pagliuzza Khader Ghneim Anum Khan Emily Ryan Justin L Harper Colin T King Sarah Welbourn Luca Micci Sol Aldrete Keith A Delman Theron Stuart Michael Lowe Jason M Brenchley Cynthia A Derdeyn Kirk Easley Rafick P Sekaly Nicolas Chomont Mirko Paiardini Vincent C Marconi Increased homeostatic cytokines and stability of HIV-infected memory CD4 T-cells identify individuals with suboptimal CD4 T-cell recovery on-ART. |
| 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 |
article |
| author |
Maria Pino Susan Pereira Ribeiro Amélie Pagliuzza Khader Ghneim Anum Khan Emily Ryan Justin L Harper Colin T King Sarah Welbourn Luca Micci Sol Aldrete Keith A Delman Theron Stuart Michael Lowe Jason M Brenchley Cynthia A Derdeyn Kirk Easley Rafick P Sekaly Nicolas Chomont Mirko Paiardini Vincent C Marconi |
| author_facet |
Maria Pino Susan Pereira Ribeiro Amélie Pagliuzza Khader Ghneim Anum Khan Emily Ryan Justin L Harper Colin T King Sarah Welbourn Luca Micci Sol Aldrete Keith A Delman Theron Stuart Michael Lowe Jason M Brenchley Cynthia A Derdeyn Kirk Easley Rafick P Sekaly Nicolas Chomont Mirko Paiardini Vincent C Marconi |
| author_sort |
Maria Pino |
| title |
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_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_sort |
increased homeostatic cytokines and stability of hiv-infected memory cd4 t-cells identify individuals with suboptimal cd4 t-cell recovery on-art. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/067e37f438b34fd7827433be61b176ba |
| work_keys_str_mv |
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| _version_ |
1718375701211512832 |