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Aging induces severe SIV infection accompanied by an increase in follicular CD8+ T cells with overactive STAT3 signaling

Cellular & Molecular Immunology volume 19, pages 1042–1053 (2022)Cite this article

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Abstract

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.

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Acknowledgements

The work was supported by the National Key R&D Program of China (2021YFC2301703), National Natural Science Foundation of China (81771770; 81671627; U1802284; 81971548; 82071847) and National Resource Center for Non-Human Primates.

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  1. These authors contributed equally: Hong-Yi Zheng, Xue-Hui Wang, Xiao-Yan He.

Authors and Affiliations

  1. 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

    Hong-Yi Zheng, Xue-Hui Wang, Xiao-Yan He, Min Chen, Ming-Xu Zhang, Xiao-Dong Lian, Jia-Hao Song, Yan Hu, Wei Pang & Yong-Tang Zheng

  2. School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230026, China

    Xue-Hui Wang & Yong-Tang Zheng

  3. Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, 650204, China

    Xiao-Yan He, Min Chen, Ming-Xu Zhang, Xiao-Dong Lian, Jia-Hao Song, Yan Hu & Yong-Tang Zheng

  4. National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650107, China

    Yun Wang, Zheng-Fei Hu, Long-Bao Lv & Yong-Tang Zheng

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Contributions

HYZ and YTZ conceived the project; HYZ, XHW, and XYH designed and performed the core experiments; HYZ, XHW, MC, MXZ, XDL, MC YH, and JHS performed the animal experiments; HYZ analyzed the data; WP, YW, ZFH, and LBL provided critical resources; HYZ drafted the manuscript; YTZ edited the manuscript. All authors contributed intellectually and approved the manuscript.

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Correspondence to Yong-Tang Zheng.

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The authors declare that they have no competing financial interests, patents, patent applications, or material transfer agreements associated with this study.

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Zheng, HY., Wang, XH., He, XY. et al. Aging induces severe SIV infection accompanied by an increase in follicular CD8+ T cells with overactive STAT3 signaling. Cell Mol Immunol 19, 1042–1053 (2022). https://doi.org/10.1038/s41423-022-00899-6

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