A soluble form of the MHC class I-specific CD160 receptor is released from human activated NK lymphocytes and inhibits cell-mediated cytotoxicity.
CD160 is a GPI-anchored lymphocyte surface receptor in which expression is mostly restricted to the highly cytotoxic CD56(dim)CD16(+) 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.
Giustiniani
Jérôme
J
Institut National de la Santé et de la Recherche Médicale 659, University Paris XII, Faculté de Médecine de Créteil, 94000 Créteil, France.
Marie-Cardine
Anne
A
Bensussan
Armand
A
D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology; D007694:Killer Cells, Natural; D008213:Lymphocyte Activation / Q000276:immunology; D012333:RNA, Messenger; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D012995:Solubility / Q000187:drug effects
D015703:Antigens, CD; C114505:CD160 protein, human; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D019409:Interleukin-15; D012333:RNA, Messenger; D011971:Receptors, Immunologic