Background: The association of T-cells with the control of HIV infection has been well documented. In addition, several studies pointed out the role on innate immune responses in the resistance or delay to HIV disease progression. The recent description (VISCONTI study) of a group of patients, so-called post-treatment controllers (PTCs), who remains with undetectable viral load after treatment interruption despite poor CD8+T cell responses, led us to study NK cells and their relationship to HIV control.
Methods: 14 patients enrolled in the French ANRS VISCONTI cohort were studied. PTCs’ results were compared to those of Viremic patients, (VIR), natural HIV controllers (HIC), patients on ARV since acute infection (ARV) and normal blood donors (controls). All phenotypic studies were done on fresh whole blood. CD107a expression on NK cells and the ICS-based assay were done on PBMC after stimulation. NK cells were tested for their capacity to inhibit HIV infection (measured by intracellular or supernatant p24) in autologous CD4 T cells. Results obtained were compared using Wilcoxon rank sum test or by the Fisher exact testResults: Visconti patients showed significantly higher expression of CD158a, CD158b (KIR2DL2/DL3), PTC showed significantly higher expression of CD158a, CD158b (KIR2DL2/DL3), CD158b/DX9 (KIR3DL1/3DS1) and NKG2A receptors (p<0.002, p<0.001, p<0.0.01, p<0.001, respectively) with lower expression of CD160 and NKp46 (p<0.001, p<0.03, respectively) receptors compared to others groups. Activation of NK cells from PTC and ARV, measured by CD69 marker, was similar to normal donors but lower than in HIC (p<0.006) or VIR patients (p<0.001). Functional studies when NK cells were stimulated by K562 cell line showed normal levels of degranulation (CD107a marker) but higher IFN-γ production for PTC than for other groups (p<0.01). NK cells from PTCs, but not from other individuals (p<0.001), were able to reduce p24 levels when co-cultured with in vitro-infected autologous CD4 T cells.
Conclusions: NK cells from PTC had a different NK cell repertoire and higher potential to produce IFN-γ compared to HIC, Viremic patients or normal donors, but similar to those treated since primary infection. More importantly, PTC NK cells showed high capacity to control in vitro HIV infection on autologous CD4 T cells. Our results suggest that preserving NK cell phenotype and function during acute infection is important to control HIV and identify NK cells as possible important agents in the durable remission of PTC.