Successfully treated HIV-infected patients have differential expression of NK cell receptors (NKp46 and NKp30) according to AIDS status at presentation

Abstract

Differences in innate immune responses may be associated with different capabilities of controlling HIV infection, not necessarily reflected by CD4+ T-cell counts alone. We investigated by cytofluorometry the expression of NK cell receptors and ligands in 19 treated HIV-infected patients with CD4+<220ml–1 at presentation (11 AIDS, 8 non-AIDS) and 10 healthy donors. Expression of NKp46 and NKp30 was significantly higher in non-AIDS vs. AIDS patients. Overall, the level of NKp46 expression directly correlated with the degree of NK cell cytotoxicity. As compared to healthy donors, in both groups, there was a similar increase of CD69 and HLA-DR expression in NK cells that directly correlated with the presence of activation markers (HLA-DR) on CD4+ and CD8+ T cells. As compared to AIDS, in non-AIDS patients in vitro activated CD4+ showed higher expression of MIC-A (NKG2D ligand), with significantly higher Nectin-2/DNAM-1 and MIC-A/NKG2D ratios. Thus, NK cell responses in AIDS and non-AIDS patients with similar CD4+ counts significantly differ despite similar treatment. This suggests an involvement of innate mechanisms, in preventing AIDS-defining opportunistic infections in HIV infection and further suggests, that CD4+ absolute counts alone, may be inadequate to explain differences in the clinical outcome.