The combination of anti-CD40L mAb and sirolimus promotes early donor skin graft tolerance
Treatment . | Donor graft acceptance rate when skin grafted at . | |
---|---|---|
1 mo . | 3 mo . | |
Hamster IgG | 0/6 | 0/20 |
Anti-CD40L | 0/3 | 15/277-150 |
Anti-CD40L + sirolimus | 6/67-150,7-151 | 5/57-150 |
Anti-CD40L + CsA | 1/8 | 7/187-150 |
Anti-CD40L + tacrolimus | 0/4 | 1/27-152 |
Treatment . | Donor graft acceptance rate when skin grafted at . | |
---|---|---|
1 mo . | 3 mo . | |
Hamster IgG | 0/6 | 0/20 |
Anti-CD40L | 0/3 | 15/277-150 |
Anti-CD40L + sirolimus | 6/67-150,7-151 | 5/57-150 |
Anti-CD40L + CsA | 1/8 | 7/187-150 |
Anti-CD40L + tacrolimus | 0/4 | 1/27-152 |
B6 mice were irradiated with 200 cGy TBI on day − 1 and infused with 40 × 106 BALB/c BM on day 0. Reagents were administered from day − 1 through day 14. Peripheral blood leukocytes of all mice were typed for percentage of donor engraftment prior to skin grafting. No hamster IgG–treated mice had any evidence of donor engraftment. All other mice had similar engraftment levels (approximately 50%-60% donor) at the time of skin grafting. Skin grafts were placed at either 1 month or at greater than 3 months after transplantation. Shown is the number of mice accepting donor skin grafts for greater than 6 months. There were no differences between groups in time to rejection in those mice that did not accept grafts. All mice promptly rejected third-party B10.BR skin grafts by 3 weeks after grafting (data not shown).
P < .001 compared with hamster IgG.
P = .003 compared with anti-CD40L as a single agent.
In contrast to other groups, tacrolimus-treated mice had poor long-term survival, greatly limiting the numbers of healthy mice available for late skin grafting. Anti-CD40L versus anti-CD40L + sirolimus at 3 months; P = .059.