NK cells of HIV-1-infected patients with poor CD4+ T-cell reconstitution despite suppressive HAART show reduced IFN-γ production and high frequency of autoreactive CD56bright cells

Abstract

HIV-1-infected patients failing to recover CD4⁺ T-cell count despite HAART (immunological non-responders, NRs), are at increased risk of disease progression and death. To better understand the NR status, we performed a comprehensive assessment of NK cells in NR patients as compared to immunologic responders. NRs exhibited an accumulation of CD56^bright NK cells inversely correlated with CD4⁺ counts. Both CD56^bright and CD56^dim NK cells of NRs displayed unimpaired degranulation ability, but poorly responded to cytokine stimulation in terms of NKp44 up-regulation and IFN-γ production that may explain the susceptibility of NRs to infections and tumors. Notably, CD56^bright NK cells from NRs showed higher cytotoxicity against autologous activated CD4⁺ T cells. Moreover, NRs had reduced Treg cell counts that showed an inverse correlation with autoreactive CD56^bright cells. These data suggest that accumulation of CD56^bright NK cells, possibly linked to decreased homeostatic control by Tregs, contributes to poor immune reconstitution in NRs.

Keywords: CD56(bright) NK cells; Cytotoxicity; HIV-1; IFN-γ; Immunological non-responders; Treg cells.