A decreased proportion of na&#239;ve MAIT cells is associated with the incomplete immune reconstitution in antiretroviral therapy-treated HIV-1 patients

Jie Jia; Hong-Yi Zheng; Yu Zhao; Kai-Cheng Gao; Deshenyue Kong; Danfeng Lu; Ji-Qun Yang; Jun-Hong Mao; Xiuwen Wang; Kun-Hua Wang; Bin Su; Jian-Hua Wang; Yong-Tang Zheng; Yi-Qun Kuang

doi:10.1016/j.virs.2025.12.003

December 2025

Citation: Jie Jia, Hong-Yi Zheng, Yu Zhao, Kai-Cheng Gao, Deshenyue Kong, Danfeng Lu, Ji-Qun Yang, Jun-Hong Mao, Xiuwen Wang, Kun-Hua Wang, Bin Su, Jian-Hua Wang, Yong-Tang Zheng, Yi-Qun Kuang. A decreased proportion of naïve MAIT cells is associated with the incomplete immune reconstitution in antiretroviral therapy-treated HIV-1 patients .VIROLOGICA SINICA, 2025, 40(6) : 962-976. http://dx.doi.org/10.1016/j.virs.2025.12.003

A decreased proportion of naïve MAIT cells is associated with the incomplete immune reconstitution in antiretroviral therapy-treated HIV-1 patients

Jie Jia ^a,b ,
Hong-Yi Zheng ^c ,
Yu Zhao ^a,b ,
Kai-Cheng Gao ^a,b ,
Deshenyue Kong ^d ,
Danfeng Lu ^d ,
Ji-Qun Yang ^e ,
Jun-Hong Mao ^d ,
Xiuwen Wang ^f ,
Kun-Hua Wang ^d,g ,
Bin Su ^{f
,,} ,
Jian-Hua Wang ^{h
,,} ,
Yong-Tang Zheng ^{c
,,} ,
Yi-Qun Kuang ^{a,b
,,}

a. Research Center for Clinical Medicine, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China;
b. Yunnan Key Laboratory of Stem Cell and Regenerative Medicine, Kunming Medical University, Kunming, 650500, China;
c. State Key Laboratory of Genetic Evolution & Animal Models, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, 650223, China;
d. NHC Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming 650032, China;
e. Third People's Hospital of Kunming City/Drug Rehabilitation Hospital of Kunming City, Kunming 650041, China;
f. Beijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China;
g. School of Life Science, Yunnan University, Kunming 650500, China;
h. Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China

Corresponding author: Bin Su, binsu@ccmu.edu.cn
Jian-Hua Wang, wang_jianhua@gibh.ac.cn
Yong-Tang Zheng, zhengyt@mail.kiz.ac.cn
Yi-Qun Kuang, kuangyiqun@kmmu.edu.cn
Received Date: 31 August 2025
Accepted Date: 02 December 2025
Available online: 04 December 2025

Abstract

Incomplete immune reconstitution occurs in 10%-40% of antiretroviral therapy (ART)-treated human immunodeficiency virus (HIV) patients. This subset of immunological non-responders (INRs) has yet to undergo a comprehensive analysis of immunological profiles, and no definitive cytological diagnosis has been established. In this study, we comparatively analyzed the immunological profiles of INRs, immunological responders (IRs), and healthy control individuals (HCs) via single-cell RNA sequencing (scRNA-seq) and single-cell T-cell receptor (TCR) repertoire sequencing of peripheral blood mononuclear cells (PBMCs), and identified a relatively small population of mucosal-associated invariant T (MAIT) cells in INRs. This finding was recapitulated in rhesus macaques infected with simian immunodeficiency virus (SIV). Specifically, the population of the naïve MAIT cell subtype was significantly lower in INRs than in IRs, and the majority of MAIT cells were CD8⁺ cell subsets. Further characteristic analysis of MAIT cells via the transcriptome revealed decreased expression of cytotoxicity-related genes in INRs, while displaying increased expression of genes involved in TGF-β receptor signaling. In summary, by conducting a comparative analysis, this study revealed a correlation between the decreased proportion of naïve MAIT cells and impaired immune reconstitution in INRs. This finding highlights a particular cell subset that may play a pivotal role in the incomplete immune reconstitution, and suggests a plausible cellular target for the modulation of INRs.
- Human immunodeficiency virus (HIV)
- , Immune reconstitution
- , Immunological response
- , T-cell receptor repertoire
- , Single-cell RNA sequencing

Electronic Supplementary Material

10.1016j.virs.2025.12.003-ESM1.docx
10.1016j.virs.2025.12.003-ESM3.xlsx
10.1016j.virs.2025.12.003-ESM2.xls

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