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* Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112;
Department of Microbiology, Tropical Medicine and Immunology, George Washington University, Washington, DC 20037; and
Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756
Recent studies have shown that NK-dendritic cell (DC) interaction plays an important role in the induction of immune response against tumors and certain viruses. Although the effect of this interaction is bidirectional, the mechanism or molecules involved in this cross-talk have not been identified. In this study, we report that coculture with NK cells causes several fold increase in IL-12 production by Toxoplasma gondii lysate Ag-pulsed DC. This interaction also leads to stronger priming of Ag-specific CD8+ T cell response by these cells. In vitro blockade of NKG2D, a molecule present on human and murine NK cells, neutralizes the NK cell-induced up-regulation of DC response. Moreover, treatment of infected animals with Ab to NKG2D receptor compromises the development of Ag-specific CD8+ T cell immunity and reduces their ability to clear parasites. These studies emphasize the critical role played by NKG2D in the NK-DC interaction, which apparently is important for the generation of robust CD8+ T cell immunity against intracellular pathogens. To the best of our knowledge, this is the first work that describes in vivo importance of NKG2D during natural infection.
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 supported by National Institutes of Health Grants AI33325 (to I.A.K.) and AI41930 (to D.J.B.).
2 Address correspondence and reprint requests to Dr. Imtiaz A. Khan, Department of Microbiology, Immunology, and Tropical Medicine, George Washington University Medical Center, Ross Hall, 2300 I Street, Washington, DC 20037. E-mail address: mtmixk{at}gwumc.edu
3 Abbreviations used in this paper: DC, dendritic cell; p.i., postinfection; TLA, Toxoplasma lysate Ag.
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