Abstract
Introduction: β7 Integrins mediate homing and retention of lymphocytes to the normal and inflamed small bowel. In the present study, we investigated the expression of β7 integrins after small bowel transplantation (SBT) and tested the immunosuppressive efficacy of blocking β7-mediated pathways through knockout or monoclonal antibodies. Methods: Heterotopic SBT from BALB/c to C57BL/6 (B6) was used as a surgical model. The expression of β7 integrins was measured on recipient lymphocytes (CD4+ and CD8+) in spleen, blood, and mesenteric lymph nodes (MLN) by flow cytometry. To analyse the effects of blocking β7 on graft survival, either β7-deficient B6 or wild-type B6 mice that were treated with monoclonal antibodies against β7 (mAb) were assessed. The course and endpoint of rejection were determined macroscopically and histologically. Results: After allogeneic SBT, there was a marked increase of α4β7high recipient CD8+ lymphocytes in MLN and blood as early as 3 days postoperatively. Integrin levels in isograft recipients were similar to those of normal mice. Median survival of intestinal allografts was not affected by β7 deficiency (7 days) compared to wild-type mice (7.5 days), but mAb significantly prolonged graft survival (12.5 days). Conclusion: As indicated by the early increase of α4β7high population, this integrin appears to play a significant role in SBT allograft rejection. The discrepancy in survival data obtained by mAb and β7 deficiency may be due to more rapid activation of compensatory mechanisms in the knockout mice.
Published Version
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