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Longitudinal association of cytokine-producing CMV-specific T cells with frailty in HIV-infected and -uninfected men who have sex with men
BACKGROUND: Chronic cytomegalovirus (CMV) infection has been postulated as a driver of chronic inflammation that has been associated with frailty and other age-related conditions in both HIV-infected (HIV+) and -uninfected (HIV-) people. METHODS: To study the T cell response to CMV as a predictor of...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8900335/ https://www.ncbi.nlm.nih.gov/pubmed/35255947 http://dx.doi.org/10.1186/s12979-022-00270-3 |
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author | Zhang, Weiying Li, Huifen Bream, Jay H. Nilles, Tricia L. Leng, Sean X. Margolick, Joseph B. |
author_facet | Zhang, Weiying Li, Huifen Bream, Jay H. Nilles, Tricia L. Leng, Sean X. Margolick, Joseph B. |
author_sort | Zhang, Weiying |
collection | PubMed |
description | BACKGROUND: Chronic cytomegalovirus (CMV) infection has been postulated as a driver of chronic inflammation that has been associated with frailty and other age-related conditions in both HIV-infected (HIV+) and -uninfected (HIV-) people. METHODS: To study the T cell response to CMV as a predictor of onset and maintenance of frailty, baseline CMV-specific T cell responses of 42 men (20 HIV-, 22 HIV+; 21 frail, 21 nonfrail) in the Multicenter AIDS Cohort Study (MACS) were assessed by flow cytometric analysis of cytokine production (IFN-γ, TNF-⍺, and IL-2) in response to overlapping peptide pools spanning 19 CMV open reading frames. The Fried frailty phenotype was assessed at baseline and semiannually thereafter. Times to transition into or out of frailty were compared by tertiles of percentages of cytokine-producing T cells using Kaplan-Meier estimators and the exact log-rank test. RESULTS: Over a median follow-up of 6.5 (interquartile range: 2) years, faster onset of frailty was significantly predicted by higher (HIV- men) or lower (HIV+ men) percentages of CD4 T cells producing only IFN-γ (IFN-γ-single-producing (SP)), and by lower percentages of IFN-γ-, TNF-⍺-, and IL-2-triple-producing CD8 T cells (HIV- men). Greater maintenance of frailty was significantly predicted by lower percentages of both these T cell subsets in HIV- men, and by lower percentages of IFN-γ-SP CD4 T cells in HIV+ men. The antigenic specificity of IFN-γ-SP CD4 T cells was different between HIV- and HIV+ nonfrail men, as were the correlations between these cells and serum inflammatory markers. CONCLUSIONS: In this pilot study, percentages of CMV-specific T cells predicted the onset and maintenance of frailty in HIV- and HIV+ men. Predictive responses differed by HIV status, which may relate to differential control of CMV reactivation and inflammation by anti-CMV T cell responses. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12979-022-00270-3. |
format | Online Article Text |
id | pubmed-8900335 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-89003352022-03-17 Longitudinal association of cytokine-producing CMV-specific T cells with frailty in HIV-infected and -uninfected men who have sex with men Zhang, Weiying Li, Huifen Bream, Jay H. Nilles, Tricia L. Leng, Sean X. Margolick, Joseph B. Immun Ageing Research BACKGROUND: Chronic cytomegalovirus (CMV) infection has been postulated as a driver of chronic inflammation that has been associated with frailty and other age-related conditions in both HIV-infected (HIV+) and -uninfected (HIV-) people. METHODS: To study the T cell response to CMV as a predictor of onset and maintenance of frailty, baseline CMV-specific T cell responses of 42 men (20 HIV-, 22 HIV+; 21 frail, 21 nonfrail) in the Multicenter AIDS Cohort Study (MACS) were assessed by flow cytometric analysis of cytokine production (IFN-γ, TNF-⍺, and IL-2) in response to overlapping peptide pools spanning 19 CMV open reading frames. The Fried frailty phenotype was assessed at baseline and semiannually thereafter. Times to transition into or out of frailty were compared by tertiles of percentages of cytokine-producing T cells using Kaplan-Meier estimators and the exact log-rank test. RESULTS: Over a median follow-up of 6.5 (interquartile range: 2) years, faster onset of frailty was significantly predicted by higher (HIV- men) or lower (HIV+ men) percentages of CD4 T cells producing only IFN-γ (IFN-γ-single-producing (SP)), and by lower percentages of IFN-γ-, TNF-⍺-, and IL-2-triple-producing CD8 T cells (HIV- men). Greater maintenance of frailty was significantly predicted by lower percentages of both these T cell subsets in HIV- men, and by lower percentages of IFN-γ-SP CD4 T cells in HIV+ men. The antigenic specificity of IFN-γ-SP CD4 T cells was different between HIV- and HIV+ nonfrail men, as were the correlations between these cells and serum inflammatory markers. CONCLUSIONS: In this pilot study, percentages of CMV-specific T cells predicted the onset and maintenance of frailty in HIV- and HIV+ men. Predictive responses differed by HIV status, which may relate to differential control of CMV reactivation and inflammation by anti-CMV T cell responses. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12979-022-00270-3. BioMed Central 2022-03-07 /pmc/articles/PMC8900335/ /pubmed/35255947 http://dx.doi.org/10.1186/s12979-022-00270-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Zhang, Weiying Li, Huifen Bream, Jay H. Nilles, Tricia L. Leng, Sean X. Margolick, Joseph B. Longitudinal association of cytokine-producing CMV-specific T cells with frailty in HIV-infected and -uninfected men who have sex with men |
title | Longitudinal association of cytokine-producing CMV-specific T cells with frailty in HIV-infected and -uninfected men who have sex with men |
title_full | Longitudinal association of cytokine-producing CMV-specific T cells with frailty in HIV-infected and -uninfected men who have sex with men |
title_fullStr | Longitudinal association of cytokine-producing CMV-specific T cells with frailty in HIV-infected and -uninfected men who have sex with men |
title_full_unstemmed | Longitudinal association of cytokine-producing CMV-specific T cells with frailty in HIV-infected and -uninfected men who have sex with men |
title_short | Longitudinal association of cytokine-producing CMV-specific T cells with frailty in HIV-infected and -uninfected men who have sex with men |
title_sort | longitudinal association of cytokine-producing cmv-specific t cells with frailty in hiv-infected and -uninfected men who have sex with men |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8900335/ https://www.ncbi.nlm.nih.gov/pubmed/35255947 http://dx.doi.org/10.1186/s12979-022-00270-3 |
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