The existence of HIV reservoirs represents the main obstacle to cure HIV. The role of the immune system at maintaining and regulating this viral persistence remains largely unknown. Here, we studied the role of the myeloid-derived suppressor cells (MDSC), a heterogeneous population of immature myeloid cells with high immunosuppressive effects on the HIV reservoir.
Samples from n=14 ART-suppressed and n=8 heathy controls were included in this study. Frequency of two subpopulation of MDSC (CD3-, CD33+, CD11b+, HLA-DRlow), M-MDSC (CD14+) and G-MDSC (CD14-), was assessed by multiparametric flow cytometry, as well as immune activation in CD4+ and CD8+ T cells (markers CD38 and HLA-DR). The functional status of MDSC was assessed by the expression of Indoleamine 2,3-dioxygenase (IDO) and Arginase-1 (ARG-1). Total HIV-DNA and intracellular HIV-RNA were quantified by qPCR in purified CD4+ T cells. P24 expression and MDSC infiltration in B-cell follicles within lymph nodes of n=2 chronic infected patients was measured by immunohistochemistry.
ART-suppressed patients presented significantly higher proportions of M-MDSC compared to healthy controls (0.24% and 0.78 in healthy and ART-suppressed donors, respectively). Importantly, this expanded M-MDSC population showed higher expression of IDO and ARG-1 (MFI of 488 and 628 for IDO, 533 and 685 for ARG-1 in healthy controls and ART-suppressed, respectively), two enzymes highly related with the immunosuppressive capacity of the MDSC. Moreover, the percentage of M-MDSC in ART-suppressed patients positively correlated with the activation of CD4+ and CD8+ T cells (rho=0.830 p=0.0008 for CD4+, and rho=0.741 p=5495 for CD8+), which in turn correlated with intracellular HIV-DNA (rho=0.742 p=0.0140 for CD4+, and rho=0.672 and p=0.0331 for CD8+) and HIV-RNA (rho=0.837 p=0.0095 for CD4+, and rho=0.877 and p=0.0042 for CD8+). Additionally, infiltration of MDSC in B-cell follicles was preferentially observed in association with the expression of p24 (rho=0.372 p=0.039).
Overall, in ART-suppressed patients, MDSC might be an important player in the preservation of the HIV-reservoir. Finding new therapeutic strategies to modulate the immunosuppressive actions of the MDSC might significantly impact the HIV reservoir.