CELL AND MAJOR HISTOCOMPATIBILITY COMPLEX REQUIREMENTS FOR OBLITERATIVE AIRWAY DISEASE IN HETEROTOPICALLY TRANSPLANTED MURINE TRACHEAS

Background. One third of human lung allografts develop chronic rejecti on manifested as obliterative bronchiolitis. Heterotopically transplan ted allogeneic murine tracheas develop obliterative airway disease (OA D) leading to a lesion resembling human obliterative bronchiolitis. Th e purpose of this study was to determine the T-cell and major histocom patibility complex (MHC) molecule requirements of murine OAD. Methods. BALB/c allografts and C57BL/6 (B6) isografts were transplanted into B 6 severe combined immunodeficient (SCID) and B6 wild-type (WT) recipie nts. MHC class I-discrepant bm1 grafts, class II-discrepant bm12 graft s, and Fl(bm1xbm12) (F1) grafts also mere transplanted into B6 WT reci pients. Grafts were harvested between days 5 and 56 following transpla ntation and evaluated histologically. Results. Complete MHC-disparate allografts placed in WT recipients had significantly more disease than similar allografts in SCID recipients, and the latter were indistingu ishable from isografts in either WT or SCID recipients, indicating a l ymphocyte dependence on the disease development. Pathology was signifi cantly more severe in bm1 and F1 allografts than in isografts recovere d from B6 recipients, but bm12 allografts appeared no different than i sografts. T-cell infiltrates in these bm12 allografts contained only C D4(+) cells, whereas infiltrates in the BALB/c, bm1, and Fl allografts manifesting OAD contained both CD4(+) and CD8(+) cells. No grafts had significant B-cell infiltration. Conclusions. These findings suggest that OAD relies on a host T-cell response that includes CD8(+) cells, directed against allo class I-bearing donor cells within the graft.