HIV controllers have activated NK cells with a particular NK cell receptor profile and higher degranulation capacity

Background: Natural killer (NK) cells are associated with the innate immune response and are important in the control of many viral infections including human immunodeficiency virus type 1 (HIV-1) infection. We studied the repertoire and function of NK cells in HIV-1-infected controllers (HIC) individuals, who maintain a clinically undetectable HIV viral load without treatment and we compared them to HIV infected viremic patients (VIR) and normal blood donors (ND).
Methods: Twenty-eight patients enrolled in the French ANRS CO18 HIV Controllers(HIC) cohort and infected by HIV-1 for >10 years who had never received antiretroviral treatment and in whom >90% of plasma HIV RNA load tests gave values < 400 copies per milliliter were studied. All phenotypic studies were done on fresh whole blood using a LSR II cytometer.CD107a expression on NK cells and the ICS-based assay were done on PBMC isolated from fresh whole blood and incubated with the target cell line K562. Associations between groups were compared using Wilcoxon rank sum test and by the Fisher exact test otherwise.
Results: HIC patients showed higher expression of CD158e (KIR3DL1/ KIR3DS1), DX9 (KIR3DL1), and NKp44 receptors compared to VIR patients or ND individuals suggesting a functional activation phenotype. Accordingly, degranulation capacity and production of IFN-γ was higher in HIC individuals. Unexpectedly, HIC individuals have lower expression of NKG2D receptor on NK cells than control groups. Degranulation and NKp46 expression were positively correlated to CD8 T cell-mediated HIV viral replication suppression capacity whereas NKG2D expression was negatively correlated. The CD8 suppression assay was done in cocultures of HIV infected CD4 T and CD8 T cells.
Conclusions: These results pointed out the cooperation between innate and adaptive immunity in HIC individuals and suggest a role of NK cells in the maintaining of HIV CD8 T cell responses in HIC individuals.

D. Celine1, P. Vermisse1, F. Boufassa2, A. Venet3, A. Saez-Cirion1, F. Barré-Sinoussi1, O. Lambotte4, D. Scott-Algara1, ANRS EP36 HIV Controllers Study Group
1Institut Pasteur, Virology, Paris, France, 2INSERM, Centre de Recherche en Epidémiologie et Santé des Populations CESP U1018, Le Kremlin-Bicêtre, France, 3INSERM U1012, Le Kremlin-Bicêtre, France, 4Hôpital Bicêtre, Internal Medicine and Infectious Diseases, Le Kremlin-Bicêtre, France