Complete replacement of tracheal epithelia by the host promotes spontaneous acceptance of orthotopic tracheal allografts in rats

Abstract 

Background

Tracheal immunogenicity has been controversial. Although replacement of allotracheal epithelia by the host epithelia has been reported in rat orthotopic tracheal grafting, the immunological effect of epithelial replacement is still uncertain.

Methods

We performed orthotopic tracheal grafting of nine cartilage rings in the following groups: 1, Lewis → Lewis (n = 30); 2, ACI → DA (n = 25); 3, Lewis → F344 (n = 23); 4-A, DA → Lewis (n = 41); 4-B, DA → Lewis with tacrolimus therapy (1 mg/kg/d for 10 days) starting from the day of the operation (n = 31); 4-C, retransplantation of DA allografts to secondary naive Lewis rats 10 or 15 days after primary grafting (n = 11); 4-D, DA → Lewis with tacrolimus therapy starting from postoperative day 10 (n = 6). Survival times and histopathology were assessed. Epithelial replacement was evaluated by immunohistochemistry.

Results

All rats survived in groups 1, 2, and 3. Even in the fully histoincompatible group 4-A, survival ratio on day 120 was 15%. Epithelial replacement was in progress on day 10 in this group. However, all tacrolimus-treated rats died by day 54 and epithelial replacement did not occur on days 30 and 50 in group 4-B. In group 4-C, retransplantation after complete epithelial replacement increased the long-surviving rats. In group 4-D, all rats receiving tacrolimus therapy after complete epithelial replacement survived over 120 days.

Conclusions

These results suggest that complete replacement of tracheal epithelia by the host promotes spontaneous acceptance of orthotopic tracheal allografts in rats.