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

Philipp Adams; Virginie Fievez; Rafaëla Schober; Mathieu Amand; Gilles Iserentant; Sofie Rutsaert; Géraldine Dessilly; Guido Vanham; Fanny Hedin; Antonio Cosma; Michel Moutschen; Linos Vandekerckhove; Carole Seguin-Devaux

doi:10.1016/j.isci.2020.101881

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

iScience. 2020 Nov 30;24(1):101881. doi: 10.1016/j.isci.2020.101881. eCollection 2021 Jan 22.

Authors

Affiliations

¹ Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette 4354, Luxembourg.
² Department of Biomedical and Clinical Sciences, Institute of Tropical Medicine, Antwerp 2000, Belgium.
³ Department of Biomedical Sciences, University of Antwerp, Antwerp 2000, Belgium.
⁴ HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University, Ghent 9000, Belgium.
⁵ AIDS Reference Laboratory, Catholic University of Louvain, Brussels 1348, Belgium.
⁶ Quantitative Biology Unit, National Cytometry Platform, Luxembourg Institute of Health, Esch-sur-Alzette L-4354, Luxembourg.
⁷ Department of Infectious Diseases, University of Liège, CHU de Liège, Liège 4000, Belgium.

Abstract

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.

Keywords: Cell Biology; Immunology; Molecular Biology; Virology.