Limited restoration of T cell subset distribution and immune function in older people living with HIV-1 receiving HAART

Abstract Background Older people living with HIV-1 (PLWH) experience a dual burden from the combined effects of aging and HIV-1 infection, resulting in significant immune dysfunction. Despite receiving HAART, immune reconstitution is not fully optimized. The objective of this study was to investigat...

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Main Authors: Na Li, Hong-Yi Zheng, Wei Li, Xiao-Yan He, Mi Zhang, Xia Li, Ren-Rong Tian, Xing-Qi Dong, Zhi-Qiang Shen, Yong-Tang Zheng
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Immunity & Ageing
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Online Access:https://doi.org/10.1186/s12979-024-00497-2
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author Na Li
Hong-Yi Zheng
Wei Li
Xiao-Yan He
Mi Zhang
Xia Li
Ren-Rong Tian
Xing-Qi Dong
Zhi-Qiang Shen
Yong-Tang Zheng
author_facet Na Li
Hong-Yi Zheng
Wei Li
Xiao-Yan He
Mi Zhang
Xia Li
Ren-Rong Tian
Xing-Qi Dong
Zhi-Qiang Shen
Yong-Tang Zheng
author_sort Na Li
collection DOAJ
description Abstract Background Older people living with HIV-1 (PLWH) experience a dual burden from the combined effects of aging and HIV-1 infection, resulting in significant immune dysfunction. Despite receiving HAART, immune reconstitution is not fully optimized. The objective of this study was to investigate the impact of aging and HAART on T cell subsets and function in PLWH across different age groups, thereby providing novel insights into the prognosis of older PLWH. Method This study was conducted at Yunnan AIDS Care Center, China, to explore the immunological responses of old PLWH to HAART and compared with the middle-age and the younger. Blood samples were collected from 146 PLWH to analyze T cell subsets and their functions, with a particular emphasis on markers related to T cell differentiation, activation, exhaustion, inflammation, and cellular function, using multicolor flow cytometry analysis. Results Older age may have a greater effect on long-term CD4+T cell recovery. Compared with young and middle-aged PLWH, older PLWH presented distinct alterations in their immune profile, including a decline in the Naïve CD4+T and CD8+T cell subsets, an expansion of effector memory cells, and other potential immune risk phenotypes, such as activation, exhaustion, and up-regulation of aging markers. In addition, we observed a significant association between the CD4 + EM3 subset and the CD8 + EM2 subset with HIV-1 progression, independent of age, suggesting their potential as reliable markers for assessing immune reconstitution in all PLWH. Conclusion Our study extends previous findings showing that older participants exhibit a wide range of late differentiation, senescence, or exhaustion phenotypes in cells, including all the CD4+T and CD8+T subsets, consistent with an immunosenescent phenotype. This may accelerate poor immune recovery in older PLWH. Identifying new strategies to improve the immune risk phenotypes of older PLWH may help improve their immune reconstitution outcomes. The CD4 + EM3 subset and the CD8 + EM2 subset should be studied as additional markers of late presentation.
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spelling doaj-art-fbf416b1d2544cdebb75fa416fdf9c512025-01-12T12:39:46ZengBMCImmunity & Ageing1742-49332025-01-0122111910.1186/s12979-024-00497-2Limited restoration of T cell subset distribution and immune function in older people living with HIV-1 receiving HAARTNa Li0Hong-Yi Zheng1Wei Li2Xiao-Yan He3Mi Zhang4Xia Li5Ren-Rong Tian6Xing-Qi Dong7Zhi-Qiang Shen8Yong-Tang Zheng9School of Pharmaceutical Sciences, Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical UniversityState Key Laboratory of Genetic Evolution & Animal Models, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Genetic Evolution & Animal Models, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Genetic Evolution & Animal Models, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of SciencesYunnan Provincial Hospital of Infectious DiseaseYunnan Provincial Hospital of Infectious DiseaseState Key Laboratory of Genetic Evolution & Animal Models, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of SciencesYunnan Provincial Hospital of Infectious DiseaseSchool of Pharmaceutical Sciences, Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical UniversityState Key Laboratory of Genetic Evolution & Animal Models, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of SciencesAbstract Background Older people living with HIV-1 (PLWH) experience a dual burden from the combined effects of aging and HIV-1 infection, resulting in significant immune dysfunction. Despite receiving HAART, immune reconstitution is not fully optimized. The objective of this study was to investigate the impact of aging and HAART on T cell subsets and function in PLWH across different age groups, thereby providing novel insights into the prognosis of older PLWH. Method This study was conducted at Yunnan AIDS Care Center, China, to explore the immunological responses of old PLWH to HAART and compared with the middle-age and the younger. Blood samples were collected from 146 PLWH to analyze T cell subsets and their functions, with a particular emphasis on markers related to T cell differentiation, activation, exhaustion, inflammation, and cellular function, using multicolor flow cytometry analysis. Results Older age may have a greater effect on long-term CD4+T cell recovery. Compared with young and middle-aged PLWH, older PLWH presented distinct alterations in their immune profile, including a decline in the Naïve CD4+T and CD8+T cell subsets, an expansion of effector memory cells, and other potential immune risk phenotypes, such as activation, exhaustion, and up-regulation of aging markers. In addition, we observed a significant association between the CD4 + EM3 subset and the CD8 + EM2 subset with HIV-1 progression, independent of age, suggesting their potential as reliable markers for assessing immune reconstitution in all PLWH. Conclusion Our study extends previous findings showing that older participants exhibit a wide range of late differentiation, senescence, or exhaustion phenotypes in cells, including all the CD4+T and CD8+T subsets, consistent with an immunosenescent phenotype. This may accelerate poor immune recovery in older PLWH. Identifying new strategies to improve the immune risk phenotypes of older PLWH may help improve their immune reconstitution outcomes. The CD4 + EM3 subset and the CD8 + EM2 subset should be studied as additional markers of late presentation.https://doi.org/10.1186/s12979-024-00497-2HIV-1AgingT cell subsetsImmunosenescenceImmunophenotypingFlow cytometry
spellingShingle Na Li
Hong-Yi Zheng
Wei Li
Xiao-Yan He
Mi Zhang
Xia Li
Ren-Rong Tian
Xing-Qi Dong
Zhi-Qiang Shen
Yong-Tang Zheng
Limited restoration of T cell subset distribution and immune function in older people living with HIV-1 receiving HAART
Immunity & Ageing
HIV-1
Aging
T cell subsets
Immunosenescence
Immunophenotyping
Flow cytometry
title Limited restoration of T cell subset distribution and immune function in older people living with HIV-1 receiving HAART
title_full Limited restoration of T cell subset distribution and immune function in older people living with HIV-1 receiving HAART
title_fullStr Limited restoration of T cell subset distribution and immune function in older people living with HIV-1 receiving HAART
title_full_unstemmed Limited restoration of T cell subset distribution and immune function in older people living with HIV-1 receiving HAART
title_short Limited restoration of T cell subset distribution and immune function in older people living with HIV-1 receiving HAART
title_sort limited restoration of t cell subset distribution and immune function in older people living with hiv 1 receiving haart
topic HIV-1
Aging
T cell subsets
Immunosenescence
Immunophenotyping
Flow cytometry
url https://doi.org/10.1186/s12979-024-00497-2
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