Combined costimulation blockade plus rapamycin but not cyclosporine produces permanent engraftment.
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.
Li
Y
Y
Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Zheng
X X
XX
Li
X C
XC
Zand
M S
MS
Strom
T B
TB
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*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000069594:Abatacept; D020123:Sirolimus