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

- CD56bright NK cells increase in NRs, HIV+ patients with low CD4 count despite HAART.
- NK cells of NRs display normal cytotoxicity against K562 targets.
- Cytokine-induced IFN-γ production and NKp44 upregulation are reduced in NR NK cells.
- NR CD56bright cells show enhanced cytotoxicity against activated CD4+ T cells.
- Treg counts are inversely correlated with autoreactive CD56bright cells in NRs.

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 CD56bright NK cells inversely correlated with CD4+ counts. Both CD56bright and CD56dim 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, CD56bright 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 CD56bright cells. These data suggest that accumulation of CD56bright NK cells, possibly linked to decreased homeostatic control by Tregs, contributes to poor immune reconstitution in NRs.