title: CD40-ligand in primate cardiac allograft and viral immunity.
abstract: Our laboratory has studied the role of CD40 ligand (CD40L, CD154) in the primate immune response to allogenic and infectious challenges. We find that intensive early blockade of CD40L reliably attenuates acute rejection of primate cardiac allografts. Monotherapy fails to prevent late graft loss, which often occurs in association with rising antidonor antibody titers and allograft vasculopathy, despite continuing anti-CD40L therapy. In contrast, the primary humoral response to T helper dependent influenza viral antigen is inhibited during anti-CD40L therapy, and responses to subsequent immunization are blunted after discontinuation of therapy. These results are encouraging with regard to the tolerogenic potential of costimulatory blockade for specific T helper dependent antigens. However, these findings also indicate that pathogenic allograft responses in primates are probably not entirely CD40L-dependent. As such, additional immunomodulatory strategies are needed to facilitate tolerance to a transplanted organ.
authors.affiliation: Vanderbilt University Medical Center, Department of Cardiothoracic Surgery, Nashville, TN, USA. robin.pierson@mcmail.vanderbilt.edu
authors.forename: R N
authors.initials: RN
authors.lastname: Pierson
authors.forename: J E
authors.initials: JE
authors.lastname: Crowe
authors.forename: S
authors.initials: S
authors.lastname: Pfeiffer
authors.forename: J
authors.initials: J
authors.lastname: Atkinson
authors.forename: A
authors.initials: A
authors.lastname: Azimzadeh
authors.forename: G G
authors.initials: GG
authors.lastname: Miller
mesh_terms: D000069594:Abatacept; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D000918:Antibody Specificity; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand / Q000187:drug effects / Q000502:physiology*; D060908:CTLA-4 Antigen; D006082:Graft Enhancement, Immunologic; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D016027:Heart Transplantation / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D018796:Immunoconjugates; D007518:Isoantibodies / Q000276:immunology; D008252:Macaca fascicularis; D051379:Mice; D016038:Skin Transplantation / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013997:Time Factors; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous; D014611:Vaccination
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015703:Antigens, CD; D000943:Antigens, Differentiation; D019013:CD40 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D018796:Immunoconjugates; D007518:Isoantibodies; D023201:CD40 Ligand; D000069594:Abatacept