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

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.