Li Na, Zheng Hong-Yi, Li Wei, He Xiao-Yan, Zhang Mi, Li Xia, Tian Ren-Rong, Dong Xing-Qi, Shen Zhi-Qiang, Zheng Yong-Tang
School of Pharmaceutical Sciences, Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, 650500, China.
State 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 Sciences, Kunming, 650223, Yunnan, China.
Immun Ageing. 2025 Jan 8;22(1):3. doi: 10.1186/s12979-024-00497-2.
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.
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.
Older age may have a greater effect on long-term CD4T cell recovery. Compared with young and middle-aged PLWH, older PLWH presented distinct alterations in their immune profile, including a decline in the Naïve CD4T and CD8T 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.
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 CD4T and CD8T 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.
感染人类免疫缺陷病毒1型（HIV-1）的老年人（PLWH）由于衰老和HIV-1感染的综合影响而承受双重负担，导致显著的免疫功能障碍。尽管接受了高效抗逆转录病毒治疗（HAART），免疫重建仍未得到充分优化。本研究的目的是调查衰老和HAART对不同年龄组PLWH的T细胞亚群和功能的影响，从而为老年PLWH的预后提供新的见解。
本研究在中国云南省艾滋病关爱中心进行，以探讨老年PLWH对HAART的免疫反应，并与中年和年轻PLWH进行比较。采集了146名PLWH的血样，通过多色流式细胞术分析来分析T细胞亚群及其功能，特别关注与T细胞分化、激活、耗竭、炎症和细胞功能相关的标志物。
年龄较大可能对CD4T细胞的长期恢复有更大影响。与年轻和中年PLWH相比，老年PLWH的免疫谱呈现出明显变化，包括初始CD4T和CD8T细胞亚群减少、效应记忆细胞扩增以及其他潜在的免疫风险表型，如激活、耗竭和衰老标志物上调。此外，我们观察到CD4+EM3亚群和CD8+EM2亚群与HIV-1进展之间存在显著关联，且与年龄无关，这表明它们有可能作为评估所有PLWH免疫重建的可靠标志物。
我们的研究扩展了先前的研究结果，表明老年参与者在细胞中表现出广泛的晚期分化、衰老或耗竭表型，包括所有CD4T和CD8T亚群，这与免疫衰老表型一致。这可能会加速老年PLWH免疫恢复不良的情况。确定改善老年PLWH免疫风险表型的新策略可能有助于改善他们的免疫重建结果。CD4+EM3亚群和CD8+EM2亚群应作为晚期表现的额外标志物进行研究。
