HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Giustiniani, J. Articles by Bensussan, A. Search for Related Content PubMed PubMed Citation Articles by Giustiniani, J. Articles by Bensussan, A.

A Soluble Form of the MHC Class I-Specific CD160 Receptor Is Released from Human Activated NK Lymphocytes and Inhibits Cell-Mediated Cytotoxicity¹

Institut National de la Santé et de la Recherche Médicale 659, University Paris XII, Faculté de Médecine de Créteil, 94000 Créteil, France

CD160 is a GPI-anchored lymphocyte surface receptor in which expression is mostly restricted to the highly cytotoxic CD56^dimCD16⁺ peripheral blood NK subset. We previously reported that MHC class I (MHC-I) molecules bind to CD160 receptors on circulating NK lymphocytes and that this interaction triggers their cytotoxic activity and cytokine production. We also observed that CD160 surface expression on NK cells is down-modulated upon activation with PMA or IL-2. In this study, we further report that short-time incubation of NK lymphocytes with IL-15 converts the membrane-bound CD160 to a soluble form through a proteolytic cleavage involving a metalloprotease. Thus, CD160 is no longer detected at the cell surface, but can be immunoprecipitated from the NK cell culture medium. Interestingly, CD160 transcript remains highly expressed during the process of protein shedding. In addition, we demonstrate that CD160 mRNA synthesis can be induced in CD56^bright separated lymphocytes following exposure to IL-15. By producing a Flag-tagged soluble CD160 protein, we establish that its binding to MHC-I molecules results in the inhibition of the cytotoxic CD8⁺ T lymphocyte activity and of the CD160-mediated NK cell cytotoxicity. Thus, we show that activated NK lymphocytes release a soluble form of CD160 that functionally impairs the MHC-I-specific cytotoxic CD8⁺ T lymphocyte responsiveness.

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 Institut National de la Santé et de la Recherche Médicale and the Association for Cancer Research.

² Address correspondence and reprint requests to Dr. Armand Bensussan, Institut National de la Santé et de la Recherche Médicale 659, Faculté de Médecine de Créteil, 8 rue du Général Sarrail, 94010 Créteil Cedex, France. E-mail address: Armand.Bensussan{at}creteil.inserm.fr

³ Abbreviations used in this paper: PB, peripheral blood; NKR, NK receptor; MHC-I, MHC class I; ILT, Ig-like transcript; KIR, killer-cell Ig-like receptor; sCD160, soluble CD160; 1,10 PNT, 1,10 phenanthroline; MIC, MHC-I chain-related gene; PLD, phospholipase D.

This article has been cited by other articles:

				M. Rabot, H. El Costa, B. Polgar, A. Marie-Cardine, M. Aguerre-Girr, A. Barakonyi, S. Valitutti, A. Bensussan, and P. Le Bouteiller CD160-activating NK cell effector functions depend on the phosphatidylinositol 3-kinase recruitment Int. Immunol., April 1, 2007; 19(4): 401 - 409. [Abstract] [Full Text] [PDF]