Reepithelialization of orthotopic tracheal allografts prevents rejection after withdrawal of immunosuppression.
Prior work has demonstrated that immunosuppressed orthotopic tracheal allografts undergo progressive reepithelialization over a 48-day period with recipient-derived tracheal epithelium. We hypothesized that reepithelialization of tracheal allografts would prevent rejection after withdrawal of immunosuppression. BALB/c murine tracheal grafts were transplanted orthotopically into either syngeneic or allogeneic C57/BL6 recipients. The recipients were either not immunosuppressed, immunosuppressed with cyclosporine A (10 mg/kg per day) continuously, or immunosuppressed for 48 days and then withdrawn from immunosuppression. The grafts were assessed for acute and chronic rejection 10 days and 50 days after immunosuppression withdrawal. The immunosuppressed allograft recipients maintained a ciliated epithelium acutely and chronically after immunosuppression withdrawal. Ten days after immunosuppression withdrawal, there was a mild cellular infiltrate, which resolved 50 days after withdrawal. Electron microscopy, lymphocyte subpopulation assays, and lamina propria analysis demonstrated that immunosuppression withdrawal did not result in tracheal allograft rejection. In vitro and in vivo assessments did not demonstrate evidence of systemic or local immune tolerance. We conclude that reepithelialization of orthotopic tracheal allografts with recipient-derived mucosa prevents rejection of allograft segments. Tracheal transplantation may require only transient immunosuppression, which can be withdrawn after tracheal reepithelialization.
Genden
Eric M
EM
Mount Sinai School of Medicine, Dept of Otolaryngology-Head and Neck Surgery, One Gustave L. Levy Place, New York, NY 10029, USA.
Govindaraj
Satish
S
Chaboki
Houtan
H
Cleven
Heidi
H
Fedorova
Elena
E
Bromberg
Jonathan S
JS
Mayer
Lloyd
L
D000818:Animals; D016516:CD4-CD8 Ratio; D004848:Epithelium / Q000502:physiology*; D006084:Graft Rejection / Q000517:prevention & control*; D007121:Immunocompetence; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D011897:Random Allocation; D012038:Regeneration / Q000502:physiology*; D014132:Trachea / Q000473:pathology / Q000637:transplantation*; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents