Implications of accumulation of clonally expanded and senescent CD4 ⁺ GNLY ⁺ T cells in immunological non-responders of HIV-1 infection Article Swipe

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Virology Human immunodeficiency virus (HIV) Biology Medicine

Xiuhan Yang , Cheng Zhen , Huihuang Huang , Yan‐Mei Jiao , Xing Fan , Chao Zhang , Jin‐Wen Song , Songshan Wang , Chun‐Bao Zhou , Xinxin Yang , Jin‐Hong Yuan , Jiyuan Zhang , Ruonan Xu , Fu‐Sheng Wang ·

YOU? · · 2024 · Open Access · · DOI: https://doi.org/10.1080/22221751.2024.2396868 · OA: W4402317549

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.