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CD32 expressing doublets in HIV infected gut-associated lymphoid are associated with a T follicular helper cell

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Title: CD32 expressing doublets in HIV infected gut-associated lymphoid are associated with a T follicular helper cell
Authors: Thornhill, J
Pace, M
Genevieve, M
Hoare, J
Peake, S
Herrera, C
Phetsouphanh, C
Meyerowitz, J
Hopkins, E
Brown, H
Dunn, P
Olejniczak, N
Wilberg, C
Klenerman, P
Goldin, R
Fox, J
Fidler, S
Frater, J
Item Type: Journal Article
Abstract: Gut-associated lymphoid tissue (GALT) is a key location for the HIV reservoir. The observation that B-cell–T-cell doublets are enriched for CD32a (a low-affinity IgG receptor) in peripheral blood raises interesting questions, especially as these cells have been associated with HIV DNA in some studies. We sought to determine if similar doublets were present in GALT, the significance of these doublets, and their implications for the HIV reservoir. Given the importance of GALT as a reservoir for HIV, we looked for expression of CD32 on gut CD4 T cells and for evidence of doublets, and any relationship with HIV DNA in HIV + individuals initiated on antiretroviral therapy (ART) during primary HIV infection (PHI). Tonsil tissue was also available for one individual. As previously shown for blood, CD32high CD4 cells were mainly doublets of CD4 T cells and B cells, with T-cell expression of ICOS in tonsil and gut tissue. CD4 T cells associated with CD32 (compared with ‘CD32−' CD4 cells) had higher expression of follicular markers CXCR5, PD-1, ICOS, and Bcl-6 consistent with a T follicular helper (TFH) phenotype. There was a significant correlation between rectal HIV DNA levels and CD32 expression on TFH cells. Together, these data suggest that CD32high doublets are primarily composed of TFH cells, a subset known to be preferentially infected by HIV.
Issue Date: 25-Jun-2019
Date of Acceptance: 28-May-2019
URI: http://hdl.handle.net/10044/1/70036
DOI: https://dx.doi.org/10.1038/s41385-019-0180-2
ISSN: 1933-0219
Publisher: Springer Nature [academic journals on nature.com]
Journal / Book Title: Mucosal Immunology
Copyright Statement: © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: MRC DCS
British HIV Association (BHIVA)
Merck Sharp & Dohme Ltd.
Medical Research Council (MRC)
Medical Research Council
Funder's Grant Number: N/A
8101898808
MR/N001265/1
MR/N001265/1
Keywords: CHERUB investigators
Immunology
06 Biological Sciences
11 Medical and Health Sciences
Publication Status: Published online
Online Publication Date: 2019-06-25
Appears in Collections:Division of Surgery
Department of Medicine
Faculty of Medicine



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