title: Reepithelialized orthotopic tracheal allografts expand memory cytotoxic T lymphocytes but show no evidence of chronic rejection.
abstract: BACKGROUND
  Acute rejection of mouse tracheal allografts is characterized by infiltration of the lamina propria with CD4+/CD8+ T cells that leads to the destruction of the epithelium and luminal obliteration. The donor epithelium is progressively replaced by recipient-derived epithelium. Once allograft reepithelialization has occurred, immunosuppression can be withdrawn without inciting acute rejection. We hypothesize that reepithelialization will also prevent chronic rejection of the trachea after withdrawal of immunosuppression.
  
  
  METHODS
  BALB/c tracheal grafts were transplanted orthotopically into allogeneic C57BL/6 recipients. Allografted mice were nonimmunosuppressed for 10 or 100 days or immunosuppressed with cyclosporine A continuously for 50 days and then withdrawn from immunosuppression for an additional 50 days. In addition, grafts from this group were then heterotopically retransplanted into isogenic C57BL/6 or allogeneic BALB/c recipients to assess their immunogenicity.
  
  
  RESULTS
  Cyclosporine A-treated mice showed no signs of chronic rejection or priming of cellular immunity as measured by proliferation and cytokine secretion in a mixed leukocyte reaction. However, there was a notable expansion of memory CD8+ T cells specific for donor major histocompatibility complex. When these tracheal allografts were retransplanted heterotopically into C57BL/6 or BALB/c, they demonstrated reduced responses toward BALB/c and primed responses toward C57BL/6, respectively. These results suggest that the grafts express a chimeric phenotype consisting of both BALB/c and C57BL/6 antigens.
  
  
  CONCLUSIONS
  These observations suggest that long-term withdrawal of immunosuppression does not lead to chronic tracheal rejection even in the presence of alloantigen specific cytotoxic T-lymphocyte responses and that the reepithelialized grafts may contain donor elements that impact the generation of immunity.
authors.affiliation: Mount Sinai School of Medicine, Department of Microbiology, New York, New York 10029, USA.
authors.forename: Heidi A
authors.initials: HA
authors.lastname: Cleven
authors.forename: Eric M
authors.initials: EM
authors.lastname: Genden
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Moran
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002908:Chronic Disease / Q000188:drug therapy; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D006084:Graft Rejection / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D006239:Haplotypes; D007156:Immunologic Memory / Q000276:immunology*; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D014019:Tissue Donors; D014132:Trachea / Q000601:surgery / Q000637:transplantation*; D014184:Transplantation, Homologous
chemical_list: D016207:Cytokines; D007519:Isoantigens; D007371:Interferon-gamma; D016572:Cyclosporine