Killer Ig-like receptor (KIR) genotype predicts the capacity of human KIR-positive CD56dim NK cells to respond to pathogen-associated signals.
IFN-gamma emanating from NK cells is an important component of innate defense against infection. In this study, we demonstrate that, following in vitro stimulation of human peripheral blood NK cells with a variety of microbial ligands, CD56(dim) as well as CD56(bright) NK cells contribute to the overall NK cell IFN-gamma response with, for most cell donors, IFN-gamma(+) CD56(dim) NK cells outnumbering IFN-gamma(+) CD56(bright) NK cells. We also observe that the magnitude of the human NK IFN-gamma response to microbial ligands varies between individuals; that the antimicrobial response of CD56(bright), but not CD56(dim), NK cells is highly correlated with that of myeloid accessory cells; and that the ratio of IFN-gamma(+) CD56(dim) to IFN-gamma(+) CD56(bright) NK cells following microbial stimulation differs between individuals but remains constant for a given donor over time. Furthermore, ratios of IFN-gamma(+) CD56(dim) to IFN-gamma(+) CD56(bright) NK cells for different microbial stimuli are highly correlated and the relative response of CD56(dim) and CD56(bright) NK cells is highly significantly associated with killer Ig-like receptor (KIR) genotype. These data reveal an influence of KIR genotype, possibly mediated via NK cell education, on the ability of NK cells to respond to nonviral infections and have implications for genetic regulation of susceptibility to infection in humans.
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Daniel S
DS
Korbel
Paul J
PJ
Norman
Kirsty C
KC
Newman
Amir
A
Horowitz
Ketevan
K
Gendzekhadze
Peter
P
Parham
Eleanor M
EM
Riley
D000942:Antigens, Bacterial / Q000276:immunology*; D019002:CD56 Antigen / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology; D005434:Flow Cytometry; D005838:Genotype; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D054340:Receptors, KIR / Q000276:immunology*
D000942:Antigens, Bacterial; D019002:CD56 Antigen; D016207:Cytokines; D054340:Receptors, KIR; D007371:Interferon-gamma