title: Transient antibody targeting of CD45RC induces transplant tolerance and potent antigen-specific regulatory T cells.
abstract: Rat and human CD4+and CD8+Tregs expressing low levels of CD45RC have strong immunoregulatory properties. We describe here that human CD45 isoforms are nonredundant and identify distinct subsets of cells. We show that CD45RC is not expressed by CD4+and CD8+Foxp3+Tregs, while CD45RA/RB/RO are. Transient administration of a monoclonal antibody (mAb) targeting CD45RC in a rat cardiac allotransplantation model induced transplant tolerance associated with inhibition of allogeneic humoral responses but maintained primary and memory responses against cognate antigens. Anti-CD45RC mAb induced rapid death of CD45RChighT cells through intrinsic cell signaling but preserved and potentiated CD4+and CD8+CD45RClow/-Tregs, which are able to adoptively transfer donor-specific tolerance to grafted recipients. Anti-CD45RC treatment results in distinct transcriptional signature of CD4+and CD8+CD45RClow/-Tregs. Finally, we demonstrate that anti-human CD45RC treatment inhibited graft-versus-host disease (GVHD) in immune-humanized NSG mice. Thus, short-term anti-CD45RC is a potent therapeutic candidate to induce transplantation tolerance in human.
authors.affiliation: Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.|Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Picarda
authors.affiliation: Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.|Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Bézie
authors.affiliation: Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.|Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Boucault
authors.affiliation: Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.|Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Autrusseau
authors.affiliation: Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.|Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Kilens
authors.affiliation: Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.|Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Meistermann
authors.affiliation: Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.|Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Martinet
authors.affiliation: Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.|Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Daguin
authors.affiliation: INSERM UMR1087, CNRS UMR6291, Université de Nantes, l'institut du thorax, Nantes, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Donnart
authors.affiliation: INSERM UMR1087, CNRS UMR6291, Université de Nantes, l'institut du thorax, Nantes, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Charpentier
authors.affiliation: Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.|Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: David
authors.affiliation: Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.|Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Anegon
authors.affiliation: Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.|Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, Nantes, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Guillonneau
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000276:immunology; D016027:Heart Transplantation; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D051379:Mice; D051381:Rats; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D023001:Transplantation Tolerance
chemical_list: D000911:Antibodies, Monoclonal; D051858:Forkhead Transcription Factors; D017493:Leukocyte Common Antigens