Elevated natural killer cell activity despite altered functional and phenotypic profile in Ugandans with HIV-1 clade A or clade D infection

Background and Objective: Natural killer (NK) cells most likely contribute toward limiting HIV-1 replication, and investigation into their function throughout the course of infection is therefore important. We here aimed to determine the state of the NK cell compartment in Ugandans with untreated HIV-1 clade A or D infection in comparison with matched uninfected controls. Methods and Results: The function and phenotype of NK cells were investigated using 10-color flow cytometry. Surprisingly, NK cells displayed elevated production of interferon-γ and macrophage inflammatory protein 1β, as well as CD107a degranulation in infected subjects. This included unexpected levels of degranulation in the CD56bright subset of NK cells and high levels of macrophage inflammatory protein 1β in CD56negative NK cells. HIV-1 infection was associated with reduced expression of KIR2DL1, NKG2A, CD161, and NKp30 in CD56dim and CD56negative NK cells, whereas lowered CD161 expression was the only alteration in the CD56bright subset. Interestingly, low CD4 counts were associated with increased levels of interferon-γ and degranulation in CD56bright NK cells, as well as increased NKp44 expression in the CD56dim cells. Conclusions: NK cells in HIV-1-infected Ugandans display elevated activity, despite an altered functional and phenotypic profile. Furthermore, specific alterations in the CD56bright and CD56dim subsets occur in patients with severe CD4 loss.