Alterations in Natural Killer Cell Receptor Profiles During HIV Type 1 Disease Progression Among Chronically Infected South African Adults

Abstract

Recent studies suggest that innate immune responses by natural killer (NK) cells play a significant role in restricting human immunodeficiency virus type-1 (HIV-1) pathogenesis. Our aim was to characterize changes in NK cells associated with HIV-1 clade C disease progression. Here we used multiparametric flow cytometry (LSRII) to quantify phenotype and function of NK cells in a cross-sectional analysis of cryopreserved blood samples from a cohort of 41 chronically HIV-1-infected, treatment-naive adult South Africans. These individuals ranged in disease severity from early (CD4 count >500) to advanced HIV-1 disease (CD4 count p < 0.05) in overall NK cell degranulation with disease progression. We found that acutely activated NK cells (CD69^pos) were deficient in NKp46 expression ex vivo. In conclusion, we observed that with viremia and advanced HIV-1 disease, activated NK cells lack NKp46 expression, and KIR2DS1^pos and/ or KIR2DL1^pos NK cells are reduced in frequency. These findings suggest that modulation of receptor expression on NK cells may play a role in HIV-1 pathogenesis, and provide new insights on immunological changes in advanced HIV-1 disease.