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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.

Original publication

DOI

10.1038/s41385-019-0180-2

Type

Journal article

Journal

Mucosal immunology

Publication Date

09/2019

Volume

12

Pages

1212 - 1219

Addresses

Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

Keywords

CHERUB investigators, Peyer's Patches, B-Lymphocytes, T-Lymphocytes, Helper-Inducer, Humans, HIV-1, HIV Infections, Receptors, IgG, CD4 Lymphocyte Count, Antiretroviral Therapy, Highly Active, Viral Load, Immunophenotyping, Gene Expression, Adult, Aged, Middle Aged, Female, Male, Biomarkers