Residual immune activation in HIV-Infected individuals expands monocytic-myeloid derived suppressor cells.

Abstract HIV-infected individuals on combined antiretroviral therapy (ART) with virologic suppression exhibit sustained immune dysfunction. Our recent work has highlighted that monocytic myeloid derived suppressor cells (M-MDSC) are elevated in these individuals and suppress immune responses. Factors responsible for M-MDSC expansion in vivo are unknown. Here we compared circulating frequency of M-MDSC in HIV-infected persons from the US and India where HIV subtype-B or –C predominate, respectively. We further investigated soluble mediators of residual immune activation in two cohorts and determined their correlation with M-MDSC expansion. Our findings show that M-MDSC are elevated and correlate with plasma levels of IL-6 in both cohorts. Chemokines CXCL10, CCL4 and CXCL8 were also elevated in HIV-infected individuals, but were not correlated with M-MDSC. These findings support that IL-6 is important in M-MDSC expansion which is independent of HIV subtype.