CD32⁺CD4⁺ memory T cells are enriched for total HIV-1 DNA in tissues from humanized mice

CD32 has raised conflicting results as a putative marker of the HIV-1 reservoir. We measured CD32 expression in tissues from viremic and virally suppressed humanized mice treated relatively early or late after HIV-1 infection with combined antiretroviral therapy. CD32 was expressed in a small fraction of the memory CD4⁺ T-cell subsets from different tissues in viremic and aviremic mice, regardless of treatment initiation time. CD32⁺ memory CD4⁺ T cells were enriched in cell-associated (CA) HIV-1 DNA but not in CA HIV-1 RNA as compared to the CD32^-CD4⁺ fraction. Using multidimensional reduction analysis, several memory CD4⁺CD32⁺ T-cell clusters were identified expressing HLA-DR, TIGIT, or PD-1. Importantly, although tissue-resident CD32⁺CD4⁺ memory cells were enriched with translation-competent reservoirs, most of it was detected in memory CD32^-CD4⁺ T cells. Our findings support that CD32 labels highly activated/exhausted memory CD4⁺ T-cell subsets that contain only a small proportion of the translation-competent reservoir.