Enrichment of the HIV reservoir in CD32+ CD4 T cells occurs early in blood and tissue

Martin, G.E.; Pace, Matthew; Thornhill, John; Phetsouphanh, Chansavath; Meyerowitz, Jodi; Gossez, Morgane; Hopkins, Emily; Brown, Helen; Robinson, Nicola; Olejniczak, Natalia; Ramjee, Gita; Kaleebu, Pontiano; Porter, Kholoud; Willberg, C; Klenerman, Paul; Nwokolo, Nneka; Fox, Julie; Fidler, Sarah; Frater, John

doi:10.1101/169342

Cited by 2 publications

(1 citation statement)

References 35 publications

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“…In initial experiments using negative selection beads, sorting CD4 T cells into CD32 + and CD32 − fractions revealed an enrichment of HIV DNA in CD32 + cells from individuals who commenced ART during PHI (clinical characteristics in Table S1 in Supplementary Material; sort strategy in Figure S7A in Supplementary Material) ( 41 ). As well as concerns detailed above over the impact of the negative selection beads, we also determined that for individuals with extremely low yields of sorted CD32 + CD3 + CD4 + cells, low cell inputs into the qPCR resulted in over-estimation of both albumin and HIV DNA (Figure S8 in Supplementary Material), which would need to be accounted for when comparing different cell populations.…”

Section: Resultsmentioning

confidence: 99%

CD32-Expressing CD4 T Cells Are Phenotypically Diverse and Can Contain Proviral HIV DNA

et al. 2018

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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.

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Section: Resultsmentioning

confidence: 99%

CD32-Expressing CD4 T Cells Are Phenotypically Diverse and Can Contain Proviral HIV DNA

et al. 2018

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CD32 Expression is not Associated to HIV-DNA content in CD4 cell subsets of individuals with Different Levels of HIV Control

García

Navarrete-Muñoz

Ligos

et al. 2018

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A recent study has pointed out to CD32a as a potential biomarker of HIV-persistent CD4 cells. We have characterized the level and phenotype of CD32+ cells contained in different subsets of CD4 T-cells and its potential correlation with level of total HIV-DNA in thirty HIV patients (10 typical progressors naïve for cART, 10 cART-suppressed patients, and 10 elite controllers). Total HIV-DNA was quantified in different subsets of CD4 T-cells: Trm and pTfh cells. Level and immunephenotype of CD32+ cells were analyzed in these same subsets by flow cytometry. CD32 expression in Trm and pTfh subsets was similar in the different groups, and there was no significant correlation between the level of total HIV-DNA and the level of CD32 expression in these subsets. However, total HIV-DNA level was correlated with expression of CD127 (rho = −0.46, p = 0.043) and of CCR6 (rho = −0.418, p = 0.027) on CD32+ cells. Our results do not support CD32 as a biomarker of total HIV-DNA content. However, analyzing the expression of certain markers by CD32+ cells could improve the utility of this marker in the clinical setting, prompting the necessity of further studies to both validate our results and to explore the potential utility of certain markers expressed by CD32+ cells.

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Enrichment of the HIV reservoir in CD32+ CD4 T cells occurs early in blood and tissue

Cited by 2 publications

References 35 publications

CD32-Expressing CD4 T Cells Are Phenotypically Diverse and Can Contain Proviral HIV DNA

CD32-Expressing CD4 T Cells Are Phenotypically Diverse and Can Contain Proviral HIV DNA

CD32 Expression is not Associated to HIV-DNA content in CD4 cell subsets of individuals with Different Levels of HIV Control

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