Background. The engineered Fc-nonbinding CD3 antibody has lower mitogenicity and a precise therapeutic window for disease remission in patients with type 1 diabetes. Before anti-CD3 can be considered for use in transplantation, the most effective timing of treatment relative to transplantation needs to be elucidated. Materials and Method. 50 Μg of anti-CD3 (145-2C11) F(ab’)₂ fragments or saline were administered intravenously for 5 consecutive days (early: day -1 to 3 or delayed: day 3 to 7) to CBA (H2_k) mice transplanted with cardiac allograft from C57Bl/10 (H2_b) (day 0). Result. Survival of allografts was prolonged in mice treated with the early protocol (MST=48 days), but most were rejected by day 100. In contrast, in mice treated with the delayed protocol allografts continued to survive long-term (Fig. 1). The delayed protocol significantly inhibited donor alloreactivity at day 30 as compared to the early protocol. A marked increase in Foxp3⁺ T cells (50.3±1.6%) infiltrating the allografts in mice treated with the delayed protocol was observed (***p<0.0001 vs. early (24.9±2.1%)) at day 10 (Fig. 2AB); a finding that was maintained in the accepted cardiac allografts at day100. We conclude that the timing of treatment with anti-CD3 therapy is critical for inducing long-term graft survival. Delaying administration effectively inhibits the alloreactivity and promotes the dominance of intragraft Foxp3⁺ T cells allowing the long-term graft acceptance.

« Back to 2013 American Transplant Congress