Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China.
School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230026, China.
Cell Mol Immunol. 2022 Sep;19(9):1042-1053. doi: 10.1038/s41423-022-00899-6. Epub 2022 Jul 18.
The number of elderly people living with HIV is increasing globally, and the condition of this population is relatively complicated due to the dual effects of aging and HIV infection. However, the impact of HIV infection combined with aging on the immune homeostasis of secondary lymphoid organs remains unclear. Here, we used the simian immunodeficiency virus mac239 (SIVmac239) strain to infect six young and six old Chinese rhesus macaques (ChRMs) and compared the infection characteristics of the two groups in the chronic stage through multiplex immunofluorescence staining of lymph nodes. The results showed that the SIV production and CD4/CD8 ratio inversion in old ChRMs were more severe than those in young ChRMs in both the peripheral blood and the lymph nodes, especially when a large number of CD8+ T cells infiltrated the follicles and germinal centers. STAT3 in these follicular CXCR5+CD8+ T cells was highly activated, with high expression of granzyme B, which might be caused by the severe inflammatory milieu in the follicles of old ChRMs. This study indicates that aging may be a cofactor involved in SIV-induced immune disorders in secondary lymphoid tissues, affecting the effective antiviral activity of highly enriched follicular CXCR5+CD8+ cells.
全球范围内，感染艾滋病毒的老年人数量正在增加，由于衰老和艾滋病毒感染的双重影响，这一人群的状况较为复杂。然而，艾滋病毒感染与衰老相结合对次级淋巴器官免疫稳态的影响尚不清楚。在这里，我们使用猴免疫缺陷病毒 mac239（SIVmac239）株感染了 6 只年轻和 6 只年老的中国恒河猴（ChRMs），并通过对淋巴结进行多重免疫荧光染色，比较了两组在慢性期的感染特征。结果表明，无论是在外周血还是淋巴结中，老年 ChRMs 的 SIV 产生和 CD4/CD8 比值反转都比年轻 ChRMs 更为严重，尤其是大量 CD8+T 细胞浸润滤泡和生发中心时。这些滤泡中的 CXCR5+CD8+T 细胞中的 STAT3 高度激活，颗粒酶 B 表达水平较高，这可能是由于老年 ChRMs 滤泡中严重的炎症环境所致。本研究表明，衰老可能是 SIV 诱导次级淋巴组织免疫紊乱的一个协同因素，影响高度富集的滤泡 CXCR5+CD8+细胞的有效抗病毒活性。
