title: Programmed death-1-programmed death-L1 interaction is essential for induction of regulatory cells by intratracheal delivery of alloantigen.
abstract: BACKGROUND
  Programmed death (PD)-1 has been implicated in peripheral tolerance. The authors investigated the roles of PD-1 and its ligands, PD-L1 and PD-L2, in the induction of regulatory cells by intratracheal delivery of alloantigen.
  
  
  METHODS
  CBA (H-2k) mice were pretreated with intratracheal delivery of C57BL/10 (H-2b) splenocytes and administration of monoclonal antibody (mAb) specific for PD-1, PD-L1, or PD-L2. Seven days later, C57BL/10 hearts were transplanted into the pretreated CBA mice. Some naive CBA mice underwent adoptive transfer of splenocytes from the pretreated CBA mice and transplantation of C57BL/10 heart.
  
  
  RESULTS
  Untreated CBA mice rejected C57BL/10 cardiac grafts acutely (median survival time [MST], 7 days). Pretreatment with intratracheal delivery of C57BL/10 splenocytes prolonged graft survival significantly (MST, 65 days). Administration of control immunoglobulin (Ig) G or anti-PD-L2 mAb did not significantly affect the prolongation (MST, 72 and 68 days, respectively). In contrast, anti-PD-1 or anti-PD-L1 mAb abrogated the prolongation (MST, 18 and 17 days, respectively). Adoptive transfer from mice pretreated with intratracheal delivery of alloantigen plus control IgG or anti-PD-L2 mAb prolonged survival of C57BL/10 grafts in secondary CBA recipients (MST, 72 and 56 days, respectively). However, concurrent administration of anti-PD-1 or anti-PD-L1 mAb abrogated prolonged survival after the adoptive transfer (MST, 14 and 20 days, respectively).
  
  
  CONCLUSIONS
  PD-1-PD-L1 interaction was essential for induction of regulatory cells by intratracheal delivery of alloantigen.
authors.affiliation: Third Department of Surgery, Nihon University, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Aramaki
authors.forename: Nozomu
authors.initials: N
authors.lastname: Shirasugi
authors.forename: Tadatoshi
authors.initials: T
authors.lastname: Takayama
authors.forename: Motohide
authors.initials: M
authors.lastname: Shimazu
authors.forename: Masaki
authors.initials: M
authors.lastname: Kitajima
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Miyuki
authors.initials: M
authors.lastname: Azuma
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Masanori
authors.initials: M
authors.lastname: Niimi
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000954:Antigens, Surface / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins / Q000276:immunology*; D002455:Cell Division / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D006085:Graft Survival; D016027:Heart Transplantation; D007519:Isoantigens / Q000008:administration & dosage / Q000276:immunology*; D008024:Ligands; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010455:Peptides / Q000276:immunology*; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D014132:Trachea
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins; C498919:Cd274 protein, mouse; D016207:Cytokines; D007519:Isoantigens; D008024:Ligands; D008562:Membrane Glycoproteins; C491383:Pdcd1 protein, mouse; C556978:Pdcd1lg2 protein, mouse; D010455:Peptides; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor