title: Combined costimulation blockade plus rapamycin but not cyclosporine produces permanent engraftment.
abstract: BACKGROUND
  Combined treatment of allograft recipients with anti-CD40 ligand and CTLA-4Ig (costimulation blockade) is a powerful promising albeit not consistently tolerizing therapy. It would be desirable to use an effective conventional immunosuppressive regimen in low doses or for a short course as an adjunct; however, cyclosporine treatment drastically blunts the ability of costimulation blockade to produce long-term engraftment.
  
  
  METHODS
  Short courses of cyclosporine or rapamycin were compared as adjuncts to costimulation blockade in the murine BALB/c to C3H/He heterotopic cardiac allograft model.
  
  
  RESULTS
  Although cyclosporine therapy blocked the capacity of costimulation blockade to produce permanent engraftment, combined rapamycin and costimulation blockade treatment produced permanent engraftment.
  
  
  CONCLUSIONS
  A theoretical basis for the differing effects of cyclosporine and rapamycin upon the outcome of costimulation blockade is forwarded. Combined use of costimulation blockade and rapamycin may provide a means to bring costimulation blockade into the clinic.
authors.affiliation: Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: X X
authors.initials: XX
authors.lastname: Zheng
authors.forename: X C
authors.initials: XC
authors.lastname: Li
authors.forename: M S
authors.initials: MS
authors.lastname: Zand
authors.forename: T B
authors.initials: TB
authors.lastname: Strom
mesh_terms: D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000627:therapeutic use*; D060908:CTLA-4 Antigen; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects; D018796:Immunoconjugates; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D020123:Sirolimus / Q000627:therapeutic use*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000069594:Abatacept; D020123:Sirolimus