title: Programmed death 1 and its ligands do not limit experimental foreign antigen-induced immune complex glomerulonephritis.
abstract: OBJECTIVE
  Interactions between the co-stimulatory molecule programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, constrain T-cell responses and help maintain peripheral tolerance. Glomerulonephritis can result from a variety of antigens, both self and foreign, and from humoural and cellular effector responses. These studies aimed to define the role of PD1 and its ligands in circulating immune complex glomerulonephritis induced by immunity to a foreign antigen.
  
  
  METHODS
  Immune complex glomerulonephritis was initiated by injecting BALB/c mice with horse spleen apoferritin intraperitoneally daily for 14 days. Inhibitory anti-mouse PD-1, anti-PD-L1 or anti-PD-L2 antibodies were administered every other day. Renal disease and immune responses were studied.
  
  
  RESULTS
  Daily injection of horse spleen apoferritin-induced proliferative immune complex glomerulonephritis in control antibody-treated mice, but inhibiting PD-1 did not augment renal injury. Specifically, blocking PD-1 did not increase serum antigen-specific antibodies or increase glomerular immunoglobulin G deposition, the hallmark of injury in this model. Furthermore, C3 deposition was unaffected and glomerular macrophages were reduced after anti-PD-1 antibodies. However, anti-PD-1 administration did increase splenocyte proliferation and cytokine production including interferon-γ, interleukin (IL)-4, and IL-17, but not IL-10. Neutralizing either PD-L1 or PD-L2 alone did not result in major alterations in renal injury.
  
  
  CONCLUSIONS
  The endogenous PD-1/PD-L pathway does not limit acute experimental foreign antigen-induced circulating immune complex glomerulonephritis.
authors.affiliation: Centre for Inflammatory Diseases, Monash University Department of Medicine, Melbourne, Victoria, Australia.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Ooi
authors.affiliation: Centre for Inflammatory Diseases, Monash University Department of Medicine, Melbourne, Victoria, Australia.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Centre for Inflammatory Diseases, Monash University Department of Medicine, Melbourne, Victoria, Australia.
authors.forename: Katerina
authors.initials: K
authors.lastname: Kourkoutzelos
authors.affiliation: Department of Immunology, Juntendo University School of Medicine.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.affiliation: Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Azuma
authors.affiliation: Centre for Inflammatory Diseases, Monash University Department of Medicine, Melbourne, Victoria, Australia.|Department of Nephrology, Monash Health, Melbourne, Victoria, Australia.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Holdsworth
authors.affiliation: Centre for Inflammatory Diseases, Monash University Department of Medicine, Melbourne, Victoria, Australia.|Department of Nephrology, Monash Health, Melbourne, Victoria, Australia.|Department of Paediatric Nephrology, Monash Health, Melbourne, Victoria, Australia.
authors.forename: A Richard
authors.initials: AR
authors.lastname: Kitching
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D000941:Antigens; D001052:Apoferritins; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007105:Immune Complex Diseases / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D000906:Antibodies; D000941:Antigens; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D016207:Cytokines; D007074:Immunoglobulin G; D018836:Inflammation Mediators; C491383:Pdcd1 protein, mouse; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D001052:Apoferritins
keywords: T-lymphocytes; antigen CD274 (programmed cell death 1 ligand 1); antigen-antibody complex; glomerulonephritis; programmed cell death 1 ligand 2 protein; programmed cell death 1 receptor (PD-1)