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Killer Ig-Like Receptor (KIR) Genotype Predicts the Capacity of Human KIR-Positive CD56^dim NK Cells to Respond to Pathogen-Associated Signals¹

Daniel S. Korbel^2,3,*, Paul J. Norman^2,, Kirsty C. Newman^2,4,*, Amir Horowitz^*, Ketevan Gendzekhadze, Peter Parham and Eleanor M. Riley^5,*

^* Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom; and Department of Structural Biology and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305

IFN- 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- response with, for most cell donors, IFN-⁺ CD56^dim NK cells outnumbering IFN-⁺ CD56^bright NK cells. We also observe that the magnitude of the human NK IFN- 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-⁺ CD56^dim to IFN-⁺ CD56^bright NK cells following microbial stimulation differs between individuals but remains constant for a given donor over time. Furthermore, ratios of IFN-⁺ CD56^dim to IFN-⁺ 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was funded by Grant GO400225 from the U.K. Medical Research Council and Grant AI017892 from the National Institutes of Health. P.J.N. was a Lymphoma Research Foundation Fellow and D.S.K. was a Boehringer Ingelheim Fonds Predoctoral Research Fellow.

D. S. K. designed the research, performed the research, analyzed data, and contributed to writing and editing of the manuscript. P. J. N. designed the research, performed the research, and analyzed data. K. C. N. designed the research, performed the research, analyzed data, and contributed to writing of the paper. A. H. performed the research and analyzed data. K. G. performed the research. P. P. designed the research, analyzed data, and contributed to writing of the paper. E. M. R. designed the research, analyzed data, and drafted and revised the paper.

² D.S.K., P.J.N., and K.C.N. contributed equally to this work.

³ Current address: Queen Mary University of London, Centre for Gastroenterology, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, 4 Newark Street, London E1 2AT, U.K.

⁴ Current address: Parliamentary Office of Science and Technology, 7 Millbank, London SW1P 3JA, U.K.

⁵ Address correspondence and reprint requests to Dr. Eleanor M. Riley, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, U.K. E-mail address: eleanor.riley{at}lshtm.ac.uk

⁶ Abbreviations used in this paper: KIR, killer Ig-like receptor; BCG, bacillus Calmette-Guérin; iRBC, infected RBC.

⁷ The online version of this article contains supplemental materials.

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The JI 2009 182: 5887-5888. [Full Text]