[en] 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.
Disciplines :
Immunology & infectious disease
Author, co-author :
Adams, Philipp; Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette 4354, Luxembourg ; Department of Biomedical and Clinical Sciences, Institute of Tropical Medicine, Antwerp 2000, Belgium ; Department of Biomedical Sciences, University of Antwerp, Antwerp 2000, Belgium
Fievez, Virginie; Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette 4354, Luxembourg
Schober, Rafaëla; Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette 4354, Luxembourg
Amand, Mathieu ; Université de Liège - ULiège > Département des sciences cliniques > GIGA-R : Immunopathologie - Maladies infectieuses et médecine interne générale ; Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette 4354, Luxembourg
Iserentant, Gilles; Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette 4354, Luxembourg
Rutsaert, Sofie; HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University, Ghent 9000, Belgium
Dessilly, Géraldine; AIDS Reference Laboratory, Catholic University of Louvain, Brussels 1348, Belgium
Vanham, Guido; Department of Biomedical and Clinical Sciences, Institute of Tropical Medicine, Antwerp 2000, Belgium ; Department of Biomedical Sciences, University of Antwerp, Antwerp 2000, Belgium
Hedin, Fanny; Quantitative Biology Unit, National Cytometry Platform, Luxembourg Institute of Health, Esch-sur-Alzette L-4354, Luxembourg
Cosma, Antonio; Quantitative Biology Unit, National Cytometry Platform, Luxembourg Institute of Health, Esch-sur-Alzette L-4354, Luxembourg
Moutschen, Michel ; Centre Hospitalier Universitaire de Liège - CHU > > Service des maladies infectieuses - médecine interne
Vandekerckhove, Linos; HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University, Ghent 9000, Belgium
Seguin-Devaux, Carole; Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette 4354, Luxembourg
CD32+CD4+ memory T cells are enriched for total HIV-1 DNA in tissues from humanized mice
Publication date :
2021
Journal title :
iScience
eISSN :
2589-0042
Publisher :
Elsevier Inc., United States
Volume :
24
Issue :
1
Pages :
101881
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
FWO - Fonds Wetenschappelijk Onderzoek Vlaanderen [BE] FNR - Fonds National de la Recherche [LU]
Funding text :
The authors would like to thank Jean-Marc Plesseria, Charlène Verschueren, Jean-Yves Servais, Christine Lambert, and Quentin Etienne for their technical support. We thank Tuesday Lowndes for revising the manuscript for English language. The study (HIV latency) was funded by a research grant from the Ministry of Research , the Fondation Recherche sur le SIDA of Luxembourg , an educational grant from ViiV Healthcare Benelux , and the FWO grant 1.8.020.09.N.00 (Linos L.V.). A.P. received a PhD AFR grant, F.V. a Mobility grant, and S.R. a PhD DTU PRIDE grant (Next-Immune) from The “Fonds National de la Recherche” in Luxembourg. R.S. received a strategic basic research fund of the Research Foundation – Flanders ( FWO , 1S32916N ) and V.L. a Collen-Francqui Research Professor Mandate.The authors would like to thank Jean-Marc Plesseria, Charl?ne Verschueren, Jean-Yves Servais, Christine Lambert, and Quentin Etienne for their technical support. We thank Tuesday Lowndes for revising the manuscript for English language. The study (HIV latency) was funded by a research grant from the Ministry of Research, the Fondation Recherche sur le SIDA of Luxembourg, an educational grant from ViiV Healthcare Benelux, and the FWO grant 1.8.020.09.N.00 (Linos L.V.). A.P. received a PhD AFR grant, F.V. a Mobility grant, and S.R. a PhD DTU PRIDE grant (Next-Immune) from The ?Fonds National de la Recherche? in Luxembourg. R.S. received a strategic basic research fund of the Research Foundation ? Flanders (FWO, 1S32916N) and V.L. a Collen-Francqui Research Professor Mandate. A.P. and F.V. setup the HIV-1 latency model in humanized mice, designed experiments, performed and analyzed all experiments, drafted figures, and wrote the manuscript; S.R. performed experiments in humanized mice and measured viral loads; A.M. performed and designed experiments in humanized mice and drafted figures; I.G. performed flow cytometry, cell sorting, cell cultures, and Flow SOM analysis; R.S. performed ddPCR assays for the measurement of CA HIV-1 RNA and CA HIV-1 DNA; D.G. setup the viral load assay; V.G. analyzed and designed the experiments; C.A. designed and conducted the multidimensional reduction analysis; H.F. performed flow SOM and cluster analysis; M.M. setup the humanized mouse model of HIV-1 infection and provided cord blood cells; V.L. designed the ddPCR studies and analyzed the results; S.-D.C designed, analyzed the data, supervised the study, and wrote the manuscript. All authors participated in the preparation and editing of the manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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