Loss of CCR7 Expression on CD56bright NK Cells Is Associated with a CD56dimCD16+ NK Cell-Like Phenotype and Correlates with HIV Viral Load

Phillip Keudel,Johanna M Eberhard,Margot Zielinska-Skowronek,Matthias Ballmaier,Henoch S Hong,Dirk Meyer-Olson,Fareed Ahmad,Golo Ahlenstiel,Reinhold E Schmidt,Nupur Bhatnagar,Benjamin A Bollmann

doi:10.1371/journal.pone.0044820

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 CD56dimCD16+ and CD56−CD16+ NK cells. However, the impact of HIV-infection on CD56bright NK cells is less well understood. Here we report a rise of CD56bright NK cells in HIV-infected individuals, which lack CCR7-expression and strongly correlate with HIV viral load. CCR7−CD56bright 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 CD56dimCD16+ NK cells. Furthermore, CD56bright 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 CD56bright NK cells, which provides a novel aspect of HIV-associated pathogenesis within the NK cell compartment.

Highlights

NK cells are effector cells of the innate immune system, which can spontaneously sense and lyse virus-infected cells [1,2]
We first assessed the expression of CCR7, CD62L, CXCR3 and CD16 on CD56bright NK cells in HIV-seronegative donors as well as in a cohort of HIV-patients, which included treated and untreated subjects
There was a substantial decrease of CCR7+ and CXCR3+ and increase of CD16+ CD56bright NK cells in untreated HIV-seropositive blood donors compared to healthy controls (Fig. 1B)

Summary

Introduction

NK cells are effector cells of the innate immune system, which can spontaneously sense and lyse virus-infected cells [1,2]. Distinct NK cell subpopulations have been described. The majority of human NK cells in peripheral blood are CD56dimCD16+ cells whereas CD56bright cells only constitute approximately 10% of the blood NK cell pool [3]. NK cell subsets seem to have distinct roles in the immune response. CD56dimCD16+ NK cells are viewed as the cytotoxic NK cell subpopulation whereas CD56bright NK cells were described to have regulatory functions by means of cytokine production, such as IFN-c and TNF among others [1,3]

Methods

Results

Conclusion