title: T-cell-based immunosuppressive therapy inhibits the development of natural antibodies in infant baboons.
abstract: BACKGROUND
  We set out to determine whether B-cell tolerance to A/B-incompatible alloantigens and pig xenoantigens could be achieved in infant baboons.
  
  
  METHODS
  Artery patch grafts were implanted in the abdominal aorta in 3-month-old baboons using A/B-incompatible (AB-I) allografts or wild-type pig xenografts (pig). Group 1 (Gp1) (controls, n=6) received no immunosuppressive therapy (IS) and no graft. Gp2 (n=2) received an AB-I or pig graft but no IS. Gp3 received AB-I grafts+IS (Gp3A: n=2) or pig grafts+IS (Gp3B: n=2). IS consisted of ATG, anti-CD154mAb, and mycophenolate mofetil until age 8 to 12 months. Gp4 (n=2) received IS only but no graft.
  
  
  RESULTS
  In Gp1, anti-A/B and cytotoxic anti-pig immunoglobulin-M increased steadily during the first year. Gp2 became sensitized to donor-specific AB-I or pig antigens within 2 weeks. Gp3 and Gp4 infants that received anti-CD154mAb made no or minimal anti-A/B and anti-pig antibodies while receiving IS.
  
  
  CONCLUSIONS
  The production of natural anti-A/B and anti-pig antibodies was inhibited by IS with anti-CD154mAb, even in the absence of an allograft or xenograft, suggesting that natural antibodies may not be entirely T-cell independent. These data are in contrast to clinical experience with AB-I allotransplantation in infants, who cease producing only donor-specific antibodies.
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Eefje M
authors.initials: EM
authors.lastname: Dons
authors.forename: Claudia
authors.initials: C
authors.lastname: Montoya
authors.forename: Cassandra E
authors.initials: CE
authors.lastname: Long
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Hara
authors.forename: Gabriel J
authors.initials: GJ
authors.lastname: Echeverri
authors.forename: Burcin
authors.initials: B
authors.lastname: Ekser
authors.forename: Corin
authors.initials: C
authors.lastname: Ezzelarab
authors.forename: Dasha Roa
authors.initials: DR
authors.lastname: Medellin
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van der Windt
authors.forename: Noriko
authors.initials: N
authors.lastname: Murase
authors.forename: Lora H
authors.initials: LH
authors.lastname: Rigatti
authors.forename: Robert
authors.initials: R
authors.lastname: Wagner
authors.forename: Roman F
authors.initials: RF
authors.lastname: Wolf
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ezzelarab
authors.forename: Lori J
authors.initials: LJ
authors.lastname: West
authors.forename: Jan N M
authors.initials: JN
authors.lastname: Ijzermans
authors.forename: David K C
authors.initials: DK
authors.lastname: Cooper
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D000961:Antilymphocyte Serum / Q000276:immunology / Q000627:therapeutic use*; D001012:Aorta, Abdominal / Q000276:immunology / Q000601:surgery; D001158:Arteries / Q000276:immunology / Q000637:transplantation; D023201:CD40 Ligand / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007166:Immunosuppressive Agents / Q000276:immunology / Q000627:therapeutic use*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000276:immunology / Q000627:therapeutic use; D010215:Papio; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology*; D014183:Transplantation, Heterologous
chemical_list: D000906:Antibodies; D000941:Antigens; D000961:Antilymphocyte Serum; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D023201:CD40 Ligand; D009173:Mycophenolic Acid