Activation of a subset of human NK cells upon contact with Plasmodium falciparum-infected erythrocytes


Artavanis-Tsakonas, K; Eleme, K; McQueen, KL; Cheng, NW; Parham, P; Davis, DM; Riley, EM; (2003) Activation of a subset of human NK cells upon contact with Plasmodium falciparum-infected erythrocytes. Journal of immunology (Baltimore, Md, 171 (10). pp. 5396-405. ISSN 0022-1767 DOI: https://doi.org/10.4049/jimmunol.171.10.5396

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Abstract

Human NK cells are the earliest source of the protective cytokine IFN-gamma when PBMC from nonimmune donors are exposed to Plasmodium falciparum-infected RBC (iRBC) in vitro. In this study, we show that human NK cells form stable conjugates with iRBC but not with uninfected RBC and that induction of IFN-gamma synthesis is dependent on direct contact between the NK cell and the iRBC. NK cells respond to iRBC only in the presence of a source of IL-12/IL-18 and the subset of NK cells that preferentially respond to iRBC express high levels of the lectin-like receptor CD94/NKG2A. There is heterogeneity between donors in their ability to respond to iRBC. DNA analysis has revealed considerable heterogeneity of killer Ig-like receptor (KIR) genotype among the donor population and has identified 21 new KIR allelic variants in the donors of African and Asian descent. Importantly, we find evidence for significant associations between KIR genotype and NK responsiveness to iRBC. This emphasizes the need for large-scale population-based studies to address associations between KIR genotype and susceptibility to malaria.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
PubMed ID: 14607943
Web of Science ID: 186643300057
URI: http://researchonline.lshtm.ac.uk/id/eprint/15703

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