Anti-CD28 mAb and rapamycin are synergistic in preventing lethal GVHD. (A) Lethally irradiated (1200 cGy) B10.BR recipients were given transplants of 15 × 106 T-cell–depleted marrow cells plus 25 × 106 splenocytes from C57BL/6 donors. Recipients were treated intraperitoneally with either anti-CD28 mAb (αCD28) at 100 μg × 1 day or rapamycin (rapamycin) at 1.5mg/kg × 14 days or both (αCD28 + rapamycin). (B) Lethally irradiated (1200 cGy) B10.BR recipients were given transplants of 15 × 106 T cell–depleted marrow cells plus 25 × 106 splenocytes from C57BL/6 donors. Recipients were treated intraperitoneally with either anti-CD28 mAb at 20 μg × 1 day or rapamycin at 1.5mg/kg × 14 days or both. (C) Lethally irradiated (1000 cGy) B10.BR recipients were given transplants of 15 × 106 T-cell–depleted marrow cells plus 15 × 106 splenocytes from C57BL/6 donors. Recipients were treated intraperitoneally with either αCD28 mAb alone or rapamycin at 1.5mg/kg × 14 days or both. Anti-CD28 mAb was given either at 100 μg × 1 day or 100 μg × 8 days, and data were combined because there was no difference in effect. Left panels show survival, and right panels show average body weight across time compared with baseline (day -1). Numbers of recipients are indicated in parentheses. Data are pooled from 2 (A) and 3 experiments (B-C), respectively.
