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NK Cells Negatively Regulate Antigen Presentation and Tumor-Specific CTLs in a Syngeneic Lymphoma Model¹

Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756

NK cells are known to kill tumor cells and produce proinflammatory cytokines that lead to the generation of tumor-specific CTLs. Many studies have used MHC class I-deficient tumor cells and/or adjuvants that induce NK cell responses. In this study, the focus was on less-immunogenic lymphoma cells that express MHC class I as a model to study NK cell responses to tumors that do not directly stimulate NK cell activation. When RMA tumor cells that expressed a truncated version of OVA, or RMA cells alone, were injected into mice that were depleted of NK cells, the mice developed an increased number of tumor-specific CTLs, increased IFN- responses, and a higher amount of Ag presentation in draining LNs compared with mice with intact NK cells. These data suggest that NK cells can inhibit the development of effective adaptive immunity in the absence of signals that trigger NK cell activation.

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 Grants CA101748 and AI07363 from the National Institutes of Health.

² Address correspondence and reprint requests to Dr. Charles L. Sentman, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, 6W Borwell Building, One Medical Center Drive, Lebanon, NH 03756. E-mail address: charles.sentman{at}dartmouth.edu

³ Abbreviations used in this paper: DC, dendritic cell; LN, lymph node.

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