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

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 studie...

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Main Authors: Thornhill, J, Pace, M, Martin, G, Hoare, J, Peake, S, Herrera, C, Phetsouphanh, C, Meyerowitz, J, Hopkins, E, Brown, H, Dunn, P, Olejniczak, N, Willberg, C, Klenerman, P, Goldin, R, Fox, J, Fidler, S, Frater, J, Cherub Investigators
Format: Journal article
Language:English
Published: Springer Nature 2019
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author Thornhill, J
Pace, M
Martin, G
Hoare, J
Peake, S
Herrera, C
Phetsouphanh, C
Meyerowitz, J
Hopkins, E
Brown, H
Dunn, P
Olejniczak, N
Willberg, C
Klenerman, P
Goldin, R
Fox, J
Fidler, S
Frater, J
Cherub Investigators
author_facet Thornhill, J
Pace, M
Martin, G
Hoare, J
Peake, S
Herrera, C
Phetsouphanh, C
Meyerowitz, J
Hopkins, E
Brown, H
Dunn, P
Olejniczak, N
Willberg, C
Klenerman, P
Goldin, R
Fox, J
Fidler, S
Frater, J
Cherub Investigators
author_sort Thornhill, J
collection OXFORD
description 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.
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spelling oxford-uuid:e9000c40-fc84-40ea-968d-951170bbf7312022-03-27T10:51:01ZCD32 expressing doublets in HIV-infected gut-associated lymphoid tissue are associated with a T follicular helper cell phenotypeJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e9000c40-fc84-40ea-968d-951170bbf731EnglishSymplectic Elements at OxfordSpringer Nature2019Thornhill, JPace, MMartin, GHoare, JPeake, SHerrera, CPhetsouphanh, CMeyerowitz, JHopkins, EBrown, HDunn, POlejniczak, NWillberg, CKlenerman, PGoldin, RFox, JFidler, SFrater, JCherub InvestigatorsGut-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.
spellingShingle Thornhill, J
Pace, M
Martin, G
Hoare, J
Peake, S
Herrera, C
Phetsouphanh, C
Meyerowitz, J
Hopkins, E
Brown, H
Dunn, P
Olejniczak, N
Willberg, C
Klenerman, P
Goldin, R
Fox, J
Fidler, S
Frater, J
Cherub Investigators
CD32 expressing doublets in HIV-infected gut-associated lymphoid tissue are associated with a T follicular helper cell phenotype
title CD32 expressing doublets in HIV-infected gut-associated lymphoid tissue are associated with a T follicular helper cell phenotype
title_full CD32 expressing doublets in HIV-infected gut-associated lymphoid tissue are associated with a T follicular helper cell phenotype
title_fullStr CD32 expressing doublets in HIV-infected gut-associated lymphoid tissue are associated with a T follicular helper cell phenotype
title_full_unstemmed CD32 expressing doublets in HIV-infected gut-associated lymphoid tissue are associated with a T follicular helper cell phenotype
title_short CD32 expressing doublets in HIV-infected gut-associated lymphoid tissue are associated with a T follicular helper cell phenotype
title_sort cd32 expressing doublets in hiv infected gut associated lymphoid tissue are associated with a t follicular helper cell phenotype
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