EFFECT OF ANTI-CD4 MONOCLONAL-ANTIBODY COMBINED WITH HUMAN CTLA4IG ONTHE SURVIVAL OF HAMSTER LIVER AND HEART XENOGRAFTS IN LEWIS RATS

We investigated the effects of pretransplant anti-CD4 monoclonal antib ody (mAb) combined with human (h) CTLA4Ig on the survival of hamster h eart and liver xenografts. Pretransplant anti-CD4 mAb (5 mg/kg x 4 day s) or hCTLA4Ig (0.5 mg/rat on days 1, 3, and 5 after transplantation) treatment alone prolonged the survival of hamster liver xenografts in Lewis rats (mean survival time [MST]=10.5 days, n=6, and MST=9.0 days, n=5, respectively, compared with untreated Lewis recipients of hamste r liver grafts, MST=6.0 days, n=6). The same regimen could not prevent hamster heart xenorejection. Pretransplant anti-CD4 mAb (5 mg/kg x 4 days) combined with hCTLA4Ig (0.5 mg/rat x 4) treatments increased sur vival of hamster liver xenograft fourfold (MST=24.2 days, n=5). The cu rrent results also show that IgG in the sera from Lewis recipients of hamster liver grafts treated with anti-CD4 mAb and hCTLA4Ig was threef old reduced at 6 days after transplantation compared with untreated Le wis rats. These results suggest a synergistic effect of anti-CD4 mAb c ombined with hCTLA4Ig in a liver xenograft transplantation model.