1. Implications of accumulation of clonally expanded and senescent CD4+GNLY+ T cells in immunological non-responders of HIV-1 infection
- Author
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Xiuhan Yang, Cheng Zhen, Huihuang Huang, Yanmei Jiao, Xing Fan, Chao Zhang, Jinwen Song, Songshan Wang, Chunbao Zhou, XinXin Yang, Jinhong Yuan, Jiyuan Zhang, Ruonan Xu, and Fu-Sheng Wang
- Subjects
HIV-1 ,CD4+ GNLY+ T cells ,immunological non-responders ,highly clonally expanded ,senescent ,Infectious and parasitic diseases ,RC109-216 ,Microbiology ,QR1-502 - Abstract
Increased CD4+GNLY+ T cells have been confirmed to be inversely associated with CD4+ T cell count in immunological non-responders (INRs), however, the underlying mechanisms are unknown. This study aimed to elucidate the characteristics of CD4+GNLY+ T cells and their relationship with immune restoration. Single-cell RNA sequencing, single-cell TCR sequencing, and flow cytometry were used to analyze the frequency, phenotypes, and function of CD4+GNLY+ T cells. Moreover, Enzyme linked immunosorbent assay was performed to detect plasma cytokines production in patients. CD4+GNLY+ T cells were found to be highly clonally expanded, characterized by higher levels of cytotoxicity, senescence, P24, and HIV-1 DNA than CD4+GNLY− T cells. Additionally, the frequency of CD4+GNLY+ T cells increased after ART, and further increased in INRs, and were positively associated with the antiretroviral therapy duration in INR. Furthermore, increased IL-15 levels in INRs positively correlated with the frequency and senescence of CD4+GNLY+ T cells, suggesting that CD4+GNLY+ T cells may provide new insights for understanding the poor immune reconstitution of INRs. In conclusion, increased, highly clonally expanded, and senescent CD4+GNLY+ T cells may contribute to poor immune reconstitution in HIV-1 infection.
- Published
- 2024
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