Loss of CCR7 Expression on \(CD56^{bright}\) NK Cells Is Associated with a \(CD56^{dim}CD16^{+}\) NK Cell-Like Phenotype and Correlates with HIV Viral Load

Abstract

NK cells are pivotal sentinels of the innate immune system and distinct subpopulations in peripheral blood have been described. A number of studies addressed HIV-induced alterations of NK cell phenotype and functionality mainly focusing on \(CD56^{dim}CD16^{+}\) and \(CD56^{-} CD16^{+}\) NK cells. However, the impact of HIV-infection on \(CD56^{bright}\) NK cells is less well understood. Here we report a rise of \(CD56^{bright}\) NK cells in HIV-infected individuals, which lack CCR7-expression and strongly correlate with HIV viral load. \(CCR7^{−} CD56^{bright}\) NK cells were characterized by increased cytolytic potential, higher activation states and a more differentiated phenotype. These cells thus acquired a number of features of \(CD56^{dim}CD16^{+}\) NK cells. Furthermore, \(CD56^{bright}\) NK cells from HIV patients exhibited higher degranulation levels compared to uninfected individuals. Thus, chronic HIV-infection is associated with a phenotypic and functional shift of \(CD56^{bright}\) NK cells, which provides a novel aspect of HIV-associated pathogenesis within the NK cell compartment.