28-OR

Abstract

Aim Natural Killer (NK) cells, first in line of defense against tumors and infections are the earliest lymphocytes to recover after Hematopoietic Cell Transplantation. NK cell responses are regulated by activating and inhibitory receptors known as Killer Immunoglobulin-like Receptors (KIR). It is still not known which NK cell subsets elicit anti-cancer or anti-viral immune response and if target induced NK cell responses are influenced by KIR gene content. Here we assessed in healthy individuals whether different NK cell subsets elicit unique immune responses against different targets (leukemia cells or herpes viruses), and if this difference is a function of individual’s KIR gene content. Methods PBMNCs from 50 healthy donors were stimulated with a leukemic cell line (K562) and a herpesvirus (Epstein-Barr virus, EBV). A 5-colour flow cytometry based estimation of cytotoxicity (CD107a expression) and cytokine (IFN- γ ) production was performed for both regulatory (CD56 bright CD16 neg ) and cytolytic (CD56 dim CD16 pos ) NK cells. KIR gene content was obtained by Luminex based rSSO method. Results Unique target induced patterns of responses were observed with different NK cell subsets. K562 cells induced degranulation with or without IFN- γ production. Contrarily, EBV induced NK cells exhibited all single (IFN- γ production and degranulation alone) and bifunctional (IFN- γ production and degranulation together) responses. In contrast to cytolytic NK cells, which in general exhibited a bifunctional response against both targets, regulatory NK cells were primarily only IFN- γ producers. High number of activating KIR genes (B/x genotypes) showed significant correlation with IFN- γ production but not with degranulation. Conclusions NK cell subsets elicit unique immune responses against different targets, some of which are influenced by the KIR gene content. Assessment of post-HCT recovery of these target-specific functional NK cell subsets and their KIR content will be important for the prediction of HCT outcomes.