Aging induces severe SIV infection accompanied by an increase in follicular CD8+ T cells with overactive STAT3 signaling
Aging induces severe SIV infection accompanied by an increase in follicular CD8+ T cells with overactive STAT3 signaling
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DOI：
10.1038/s41423-022-00899-6
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发表时间：
2022-07
影响因子：
24.1
通讯作者：
Hong-yi Zheng;Xue-Hui Wang;Xiao-Yan He;Min Chen;Ming-Xu Zhang;Xiao-Dong Lian;Jia-Hao Song;Yan Hu;W. Pang;Yun Wang;Zheng-Fei Hu;Long-Bao Lv;Yongchui Zheng
中科院分区：
文献类型：
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作者：
Hong-yi Zheng;Xue-Hui Wang;Xiao-Yan He;Min Chen;Ming-Xu Zhang;Xiao-Dong Lian;Jia-Hao Song;Yan Hu;W. Pang;Yun Wang;Zheng-Fei Hu;Long-Bao Lv;Yongchui Zheng
全球感染艾滋病毒的老年人数量正在增加，由于老龄化和艾滋病毒感染的双重影响，这一人群的状况相对复杂。然而，HIV感染与衰老相结合对次级淋巴器官免疫稳态的影响仍不清楚。本研究采用猴免疫缺陷病毒mac 239株（SIVmac 239）感染6只幼龄和6只老龄中国恒河猴（ChRM），通过淋巴结多重免疫荧光染色比较两组慢性期的感染特征。结果表明，老年ChRM外周血和淋巴结中SIV的产生和CD 4/CD 8比值倒置均较年轻ChRM严重，尤其是当大量CD 8 + T细胞浸润卵泡和生殖中心时。这些滤泡CXCR 5 + CD 8 + T细胞中的STAT 3高度活化，颗粒酶B高表达，这可能是由老年ChRM滤泡中严重的炎症环境引起的。这项研究表明，衰老可能是参与SIV诱导的次级淋巴组织免疫紊乱的辅助因子，影响高度富集的滤泡CXCR 5 + CD 8+细胞的有效抗病毒活性。
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.