title: Human and mouse mast cells express and secrete the GPI-anchored isoform of CD160.
abstract: CD160 is expressed by human and mouse natural killer (NK) cells and other cytotoxic lymphocyte subpopulations. CD160 is mostly expressed as a trimeric 83 kDa glycosylphosphatidylinositol (GPI)-anchored activating NK receptor, cleaved upon IL-15 stimulation in a secreted trimeric soluble form (sCD160) that binds to major histocompatibility complex (MHC) class I molecules, while a transmembrane isoform appears. sCD160 exhibits immunoregulatory function as it inhibits CD8(+) T-lymphocyte cytotoxic activity. We show that human mast cells (MCs) express CD160. In human and mouse skin, resident MCs expressed CD160, whereas in C57BL/6-Kit(W-sh/W-sh) mice, CD160(+) cells were only identified at the site of reconstitution with syngeneic cultured MCs. In the human mast cell line, HMC-1, we only identified the transcripts of the GPI-anchored CD160 isoform. Furthermore, CD160 was identified in HMC-1 and mouse MC supernatants, suggesting that MCs release sCD160. Supporting this hypothesis, HMC-1 express the GPI-specific phospholipase D variant 2 involved in the NK lymphocyte membrane cleavage of CD160, and morphological studies highlighted a relative loss of CD160 expression in inflammatory skin sites, where MC degranulation is expected to occur. We also demonstrated an inhibition of T-cell cytotoxicity by HMC-1 supernatant that was partially reversed by anti-CD160 mAb. In conclusion, sCD160, produced by MCs, may have a role in T-cell-MC interactions in vivo.
authors.affiliation: AP-HP, Groupe Hospitalier Henri Mondor-Albert Chenevier, Department of Pathology, and Université Paris 12, Faculté de Médecine, Créteil, France. nicolas.ortonne@hmn.aphp.fr
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ortonne
authors.forename: Caroline
authors.initials: C
authors.lastname: Ram-Wolff
authors.forename: Jérôme
authors.initials: J
authors.lastname: Giustiniani
authors.forename: Anne
authors.initials: A
authors.lastname: Marie-Cardine
authors.forename: Martine
authors.initials: M
authors.lastname: Bagot
authors.forename: Salaheddine
authors.initials: S
authors.lastname: Mecheri
authors.forename: Armand
authors.initials: A
authors.lastname: Bensussan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D019556:COS Cells; D002450:Cell Communication / Q000276:immunology; D002522:Chlorocebus aethiops; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003872:Dermatitis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020405:Dermis / Q000166:cytology / Q000276:immunology; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000166:cytology; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology; D012995:Solubility
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C114505:CD160 protein, human; C511585:Cd160 protein, mouse; D017077:Culture Media, Conditioned; D058851:GPI-Linked Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic