title: Modulation of cytotoxic responses by targeting CD160 prolongs skin graft survival across major histocompatibility class I barrier.
abstract: CD160 is a glycosylphosphatidylinositol-anchored protein of the immunoglobulin superfamily. It exhibits a pattern of expression coincident in humans and mice that is mainly restricted to cytotoxic cells and to all intestinal intraepithelial T lymphocytes. B- and T-lymphocyte attenuator (BTLA) and CD160 interact with cysteine-rich domain 1 of the extracellular region of Herpesvirus entry mediator (HVEM). CD160 engagement by HVEM can deliver inhibitory signals to a small subset of human CD4 T cells and attenuate its proliferation and cytokine secretion, but can also costimulate natural killer cells or intraepithelial lymphocytes. In turn, CD160 and BTLA can also function as agonist ligands being capable of costimulating T cells through membrane HVEM. Based on the restricted pattern of CD160 expression in cytotoxic cells, we postulated that CD160 may represent a suitable target for immune intervention in the setting of transplantation to modulate allogeneic cytotoxic responses. We demonstrated that in vivo administration of anti-CD160 antibody in combination with anti-CD40 L antibody to limit CD4 T-cell help modulated cytotoxic responses in a major histocompatibility complex class I mismatched model of allogeneic skin graft transplantation (bm1 donor to C57BL/6 recipient) and significantly prolonged graft survival. The implementation of this strategy in transplantation may reinforce current immunosuppression protocols and contribute to a better control of CD8 T-cell responses.
authors.affiliation: Transplantation Immunobiology Section, University of Leon and Castilla and Leon Regional Transplantation Coordination, Leon University Hospital, Leon, Spain. Electronic address: mlriogon@saludcastillayleon.es.
authors.forename: Maria-Luisa
authors.initials: ML
authors.lastname: Del Rio
authors.affiliation: Department of Veterinary Clinical Sciences, University of Santiago de Compostela, Veterinary Faculty, Lugo, Spain.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Bravo Moral
authors.affiliation: Transplantation Immunobiology Section, University of Leon and Castilla and Leon Regional Transplantation Coordination, Leon University Hospital, Leon, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernandez-Renedo
authors.affiliation: Visceral and Transplantation Surgery, Department of Surgery, University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland.
authors.forename: Leo
authors.initials: L
authors.lastname: Buhler
authors.affiliation: Department of Hematology, University Hospital Virgen del Rocio/Institute of Biomedicine (IBIS/CSIC), Sevilla, Spain.
authors.forename: Jose-Antonio
authors.initials: JA
authors.lastname: Perez-Simon
authors.affiliation: CNRS UPR 3572, IBMC, Immunopathologie et Chimie Thérapeutique, Strasbourg, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Chaloin
authors.affiliation: Department of Molecular and Cell Biology, School of Biological Sciences, University of Leon, Leon, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Alvarez Nogal
authors.affiliation: Department of Medicine, Surgery and Veterinary Anatomy, School of Veterinary Medicine, University of Leon, Leon, Spain.
authors.forename: Maximino
authors.initials: M
authors.lastname: Fernandez-Caso
authors.affiliation: Transplantation Immunobiology Section, University of Leon and Castilla and Leon Regional Transplantation Coordination, Leon University Hospital, Leon, Spain. Electronic address: ignacio.barbosa@unileon.es.
authors.forename: Jose-Ignacio
authors.initials: JI
authors.lastname: Rodriguez-Barbosa
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology / Q000378:metabolism; D006085:Graft Survival / Q000276:immunology*; D057809:HEK293 Cells; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D006825:Hybridomas / Q000378:metabolism; D007156:Immunologic Memory; D056747:Immunomodulation; D007694:Killer Cells, Natural / Q000276:immunology; D008198:Lymph Nodes / Q000378:metabolism; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D016038:Skin Transplantation
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C511585:Cd160 protein, mouse; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D011971:Receptors, Immunologic; D023201:CD40 Ligand