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CD32-Expressing CD4 T Cells are phenotypically diverse and can contain proviral HIV DNA

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Title: CD32-Expressing CD4 T Cells are phenotypically diverse and can contain proviral HIV DNA
Authors: Martin, GE
Pace, M
Thornhill, JP
Phetsouphanh, C
Meyerowitz, J
Gossez, M
Brown, H
Olejniczak, N
Lwanga, J
Ramjee, G
Kaleebu, P
Porter, K
Willberg, CB
Klenerman, P
Nwokolo, N
Fox, J
Fidler, S
Frater, J
Item Type: Journal Article
Abstract: Efforts to both characterize and eradicate the HIV reservoir have been limited by the rarity of latently infected cells and the absence of a specific denoting biomarker. CD32a (FcγRIIa) has been proposed to be a marker for an enriched CD4 T cell HIV reservoir, but this finding remains controversial. Here, we explore the expression of CD32 on CD3+CD4+ cells in participants from two primary HIV infection studies and identify at least three distinct phenotypes (CD32low, CD32+CD14+, and CD32high). Of note, CD4 negative enrichment kits remove the majority of CD4+CD32+ T cells, potentially skewing subsequent analyses if used. CD32high CD4 T cells had higher levels of HLA-DR and HIV co-receptor expression than other subsets, compatible with their being more susceptible to infection. Surprisingly, they also expressed high levels of CD20, TCRαβ, IgD, and IgM (but not IgG), markers for both T cells and naïve B cells. Compared with other populations, CD32low cells had a more differentiated memory phenotype and high levels of immune checkpoint receptors, programmed death receptor-1 (PD-1), Tim-3, and TIGIT. Within all three CD3+CD4+CD32+ phenotypes, cells could be identified in infected participants, which contained HIV DNA. CD32 expression on CD4 T cells did not correlate with HIV DNA or cell-associated HIV RNA (both surrogate measures of overall reservoir size) or predict time to rebound viremia following treatment interruption, suggesting that it is not a dominant biomarker for HIV persistence. Our data suggest that while CD32+ T cells can be infected with HIV, CD32 is not a specific marker of the reservoir although it might identify a population of HIV enriched cells in certain situations.
Issue Date: 4-May-2018
Date of Acceptance: 16-Apr-2018
URI: http://hdl.handle.net/10044/1/60186
DOI: https://dx.doi.org/10.3389/fimmu.2018.00928
ISSN: 1664-3224
Publisher: Frontiers Media
Journal / Book Title: Frontiers in Immunology
Volume: 9
Copyright Statement: © 2018 Martin, Pace, Thornhill, Phetsouphanh, Meyerowitz, Gossez, Brown, Olejniczak, Lwanga, Ramjee, Kaleebu, Porter, Willberg, Klenerman, Nwokolo, Fox, Fidler and Frater. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY - https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
HIV
reservoir
CD32
primary HIV infection
HIV DNAIN
ANTIRETROVIRAL THERAPY
IMMUNE-RESPONSES
RESERVOIR SIZE
FC-RECEPTORS
IN-VIVO
INFECTION
EXPRESSION
ACTIVATION
PROLIFERATION
INFLAMMATION
HIV DNA
Publication Status: Published
Article Number: ARTN 928
Appears in Collections:Department of Medicine
Faculty of Medicine



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