Donor antigen–presenting cells are important in the development of obliterative airway disease

Abstract

Objective: Obliterative airway disease, which resembles obliterative bronchiolitis histologically, develops in murine heterotopic tracheal allografts. Chimeric tracheas were used to examine whether donor-type antigen-presenting cells are important in the development of obliterative airway disease. To separate the contributions of CD4+ and CD8+ direct pathways, we transplanted tracheas from knockout mice lacking major histocompatibility complex (MHC) class I or II antigens. Methods: Chimeric tracheas were created via bone marrow transplantation in fully MHC-mismatched combinations. Tracheas from naive B6, autologously reconstituted B6, chimeric B6 bearing recipient-type C3H antigen-presenting cells, MHC class I knockout B6 (B6I–), MHC class II knockout B6 (B6II–), or C3H mice were transplanted into C3H recipients. The tracheas were harvested at days 14 and 28. Results: At day 28, isografts showed no occlusion, normal respiratory epithelium, and minimal infiltrates. Naive or autologously reconstituted B6, B6I–, and B6II– tracheas showed minimal occlusion at day 14 but contained intraepithelial infiltrates. By day 28, the naive or autologously reconstituted B6 tracheas had occlusion of 69.5% ± 11.6% (mean ± standard error of the mean), and in comparison, B6I– and B6II– tracheas had occlusions of 53.0% ± 16.3% and 52.2% ± 15.9%, respectively (P = .20, .19). In chimeric B6 tracheas, minimal occlusion was seen at day 14 and remained 33.6% ± 16.2% (P = .039) at day 28. Subtle epithelial changes and minimal infiltrates were seen. Conclusions: Obliterative airway disease appears to involve donor-type antigen-presenting cells and develops in the absence of either MHC class I or II antigens. These findings suggest that either CD8+ or CD4+ direct allorecognition is important in the development of obliterative airway disease. (J Thorac Cardiovasc Surg 2000;120:1070-7)