title: Contribution of CD40-CD154-mediated costimulation to an alloresponse in vivo.
abstract: BACKGROUND
  Costimulation through CD40-CD154 plays an important role in T-cell activation. Although systemic administration of anti-CD154 antibody prevents or delays rejection of organ allografts in animal models, the molecular mechanisms responsible for this effect are not well defined.
  
  
  METHODS
  We have previously demonstrated that priming of mice (H2d) with CD40-/- but not with wildtype naive B cells (H2b) leads to alloantigen-specific T-cell hyporesponsiveness in vitro. In the present study, we investigated whether such priming modifies allograft rejection in a major histocompatibility complex-mismatched murine cardiac transplantation model.
  
  
  RESULTS
  Priming of hosts with donor-specific CD40-/- B cells delayed rejection of subsequently transplanted wild-type cardiac allografts by 8.0 days (P<0.001). The lack of CD40 on the cardiac graft delayed rejection in unprimed or primed hosts by 3-5 days. Prolongation of graft survival correlated with the failure of infused CD40-/- B cells to express B7.2 and ICAM-1 in vivo.
  
  
  CONCLUSIONS
  Our data suggest that CD40-CD154 costimulation contributes to T cell priming to alloantigens in vivo and to a second set rejection phase in which donor antigens are presented to primed T cells.
authors.affiliation: Department of Research, Basel University Medical School, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Förster
authors.forename: W
authors.initials: W
authors.lastname: Krenger
authors.forename: J
authors.initials: J
authors.lastname: Joergensen
authors.forename: R
authors.initials: R
authors.lastname: Hof
authors.forename: R S
authors.initials: RS
authors.lastname: Geha
authors.forename: G A
authors.initials: GA
authors.lastname: Holländer
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D019013:CD40 Antigens / Q000096:biosynthesis / Q000276:immunology*; D023201:CD40 Ligand; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007518:Isoantibodies / Q000096:biosynthesis*; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D019013:CD40 Antigens; D018984:Epitopes, T-Lymphocyte; D007518:Isoantibodies; D007519:Isoantigens; D008562:Membrane Glycoproteins; D018799:Intercellular Adhesion Molecule-1; D023201:CD40 Ligand