Severe rejection of rat intestinal grafts overexpressing human histo-blood group A/B transferase

Background To test the effect of overexpressed human A/B antigens on rat immunity, we have developed transgenic (Tg) rats with human blood group A/B transferase genes in a previous report. Using these rats whose intestine expressed the A/B antigen, we tested the antigenecity of overexpressed A/B antigens in intestinal tracts. Materials and methods Wild-type (MHC haplotype: RT1k) and human histo-blood A or B transferase gene transgenic (A- or B-Tg) Wistar rats were used. We tested rejection reaction in heterotopic small bowel transplantation (SBT). Then, we conducted SBT and measured changes in rat anti-human blood type A antibody titers. Results Small intestinal grafts from Tg to wild-type rats were severely rejected (A-Tg grafts, 19.8±5.6days; B-Tg grafts, 14.3±4.6days). Serologic study showed that rat anti-human A antibody was detected in both adult A- and B-Tg rats, but not in wild-type rats. Grafts from wild-type and Tg rats were more rapidly rejected in Tg rat recipients (7.9±2.9days). The rat anti-human A antibody titer in the Tg rat recipients with wild-type intestine was significantly elevated after SBT. Conclusion Rat intestinal grafts overexpressing human histo-blood group A/B transferase were severely rejected, inducing humoral antibody production.