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.

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.

Phenotypically and functionally distinct subsets contribute to the expansion of CD56-/CD16+ natural killer cells in HIV infection.

Objective: Chronic HIV infection has been associated with activation and increased turnover of natural killer (NK) cells as well as with disturbed homeostasis of the NK cell compartment, including loss of CD56(+) NK cells and accumulation of dysfunctional CD56(-)/CD16(+) NK cells. We performed a comprehensive phenotypical and functional characterization of this population.

Design: A cross-sectional study was performed to analyze CD56(-)/CD16(+) NK cells from 34 untreated HIV-infected and 15 seronegative individuals.

HIV infection is associated with a preferential decline in less-differentiated CD56dim CD16+ NK cells.

HIV-1 infection is characterized by loss of CD56(dim) CD16(+) NK cells and increased terminal differentiation on various lymphocyte subsets. We identified a decrease of CD57(-) and CD57(dim) cells but not of CD57(bright) cells on CD56(dim) CD16(+) NK cells in chronic HIV infection. Increasing CD57 expression was strongly associated with increasing frequencies of killer immunoglobulin-like receptors (KIRs) and granzyme B-expressing cells but decreasing percentages of cells expressing CD27(+), HLA-DR(+), Ki-67(+), and CD107a.