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Cutting Edge: Distinct NK Receptor Profiles Are Imprinted on CD8 T Cells in the Mucosa and Periphery during the Same Antigen Challenge: Role of Tissue-Specific Factors¹

Amale Laouar^2,*, Monika Manocha^*, Meimei Wan^*, Hideo Yagita, Rene A. W. van Lier and N. Manjunath^*

^* CBR Institute for Biomedical Research and Department of Pediatrics, Harvard Medical School, Boston, MA 02115; Juntendo University School of Medicine, Tokyo, Japan; and Academic Medical Center, Amsterdam, The Netherlands

NK cell receptors (NKRs) modulate T lymphocyte responses by modifying the Ag activation threshold. However, what governs their expression on T cells remains unclear. In this study we show that different NKRs are imprinted on CD8 T cells in the gut mucosa and periphery during the same Ag challenge. After a viral, bacterial, and tumor challenge, most CD8 peritoneal exudate lymphocytes expressed NKG2A but not 2B4. In contrast, most CD8 intraepithelial lymphocytes exhibited 2B4 but not NKG2A. Our data suggest that tissue-specific factors may determine the pattern of NKR expression. In the gut, CD70 licensing appears to promote 2B4 induction on mucosal CD8 T cells. Conversely, retinoic acid produced by the intestinal dendritic cells may suppress NKG2A expression. Thus, tissue-specific factors regulate NKR expression and may confer T cells with differing effector functions in a tissue and site-specific manner.

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 Grant AI46566 and Senior Research Award from the Crohn’s and Colitis Foundation of America (to N.M.).

² Address correspondence and reprint requests to Dr. Amale Laouar, CBR Institute for Biomedical Research, 800 Huntington Avenue, Boston. MA 02115. E-mail address: laouar{at}cbr.med.harvard.edu

³ Abbreviations used in this paper. NKR, natural killer receptor; DC, dendritic cell; IEL, intraepithelial lymphocyte; Lm, Listeria monocytogenes; LP, lamina propria; MLN, mesenteric lymph node; PEL, peritoneal exudate lymphocyte; RA, retinoic acid.

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