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 (B6(I-)), MHC class II knockout B6 (B6(II-)), 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, B6(I-), and B6(II-) 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, B6(I-) and B6(II-) 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.
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 (B6(I-)), MHC class II knockout B6 (B6(II-)), 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, B6(I-), and B6(II-) 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, B6(I-) and B6(II-) 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.