Epithelial re-growth is associated with inhibition of obliterative airway disease in orthotopic tracheal allografts in non-immunosuppressed rats

Background. Because epithelial cells are targets of alloimmune injury leadi ng ultimately to airway obliteration, we tested whether epithelial re-growt h could prevent obliterative airway disease (OAD) in orthotopic tracheal al lografts. Methods. Brown Norway tracheal segments were orthotopically transplanted in to nonimmunosuppressed Lewis rats, Allografts were removed on days 2-10 (n= 13), 30 (n=4), and 60 (n=5) for histology, computerized morphometry (oblite ration), and immunohistochemical detection of mononuclear cells, smooth mus cle alpha-actin, and tissue phenotype, Normal tracheas, host tracheas, and heterotopically transplanted allografts served as controls, Results. Orthotopic allografts removed on days 21-10 exhibited epithelial d amage and re-growth and mononuclear cell infiltration. On days 30 and 60, p artially ciliated cuboidal or attenuated epithelium completely covered the lumen. Although mononuclear cells declined, numerous T cells with a high CD 4/CD8 ratio were found in the epithelium till day 60, Orthotopic allograft epithelium expressed donor phenotype on day 7, but recipient phenotype on d ays 30 and 60, Despite subepithelial a-actin positive myofibroblast prolife ration, obliteration did not progress from day 7 to 30 and 60 (35, 30, and 33%, respectively). Although more than in normal or host tracheas, the obli teration in orthotopic allografts on days 30 and 60 was significantly less (P < 0.001) than in heterotopic allografts. Conclusions. We describe, for the first time, longterm patency of fully his toincompatible orthotopic tracheal allografts in nonimmunosuppressed rats. Despite acute alloimmune injury and induction of myofibroblast proliferatio n, epithelial re-growth from the host limited the progression of OAD, thus emphasizing the role of epithelium in the control of airway obliteration.