Abstract
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.
Highlights
The existence of HIV reservoirs is the main barrier to HIV eradication[1]
Elite controllers (EC), patients with undetectable HIV plasma viremia in the absence of antiretroviral therapy (n = 10), and treated patients (TX) (n = 10), cART-suppressed patients maintaining undetectable pVL, were not significantly different in terms of age, CD4 counts and time since HIV diagnosis, proportion of males was higher in TX compared to elite controllers (EC) group
Levels of HIV-DNA in resting memory CD4 T (Trm) and peripheral T follicular helper cells were lowest in EC patients (381 [74–1002] and 88 [73–291] copies/million cells in Trm and pTfh respectively) and highest in TP patients (6768 [3674–12673] and 7737 [4921–9044] copies/million cells in Trm and pTfh respectively), with an intermediate level in TX group (1197[619–1623] and 723 [393–1199] copies/million cells in Trm and pTfh respectively)
Summary
The existence of HIV reservoirs is the main barrier to HIV eradication[1]. At cellular level HIV latency is mainly found in CD4 T cells with a resting memory phenotype[2,3,4], especially in certain subsets such as peripheral follicular T helper cells[5]. For the understanding of cellular reservoirs and as an scalable high-throughput assay to precisely measure the in vivo frequency of latently infected cells, that could be implemented in clinical trials aimed to purge the HIV reservoir[14]. In this regard, a very recent paper has pointed to CD32a as a potential biomarker of latently infected CD4 cells[15]. The content of proviral HIV-DNA was several hundred-fold higher in purified CD4+CD32a+ compared to CD4+CD32a− cells from patients under antiretroviral therapy From these results the authors conclude that CD32a is a good potential biomarker of persistently infected cells[15]. In the present study we have characterized the levels and phenotype of CD32+ cells contained in different subsets of CD4 T-cells, and its potential correlation with total HIV-DNA content in two groups of HIV patients with HIV replication control (spontaneously or through cART) and in a group of progressor HIV patients with uncontrolled HIV replication
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