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