The effects of pretreatment with donor antigen and immunosuppressive agents on fully allogenic tracheal graft.
BACKGROUND
Obliterative bronchiolitis is a major clinical problem in cases involving a transplanted lung. We examined drug-induced tolerance to a fully allogenic tracheal graft in a murine heterotopic transplantation model.


METHODS
Recipient mice (C57BL/6) were primed iv with 1 x 10(8) splenocytes of donor mice (BALB/c). Day 0 was the day of the splenocyte injection. Cyclophosphamide and Busulfan were injected intraperitoneally on day 2. On day 3, 1 x 10(7) donor bone marrow cells were intravenously injected. On day 28, a donor tracheal graft was implanted into a subcutaneous pocket. Grafts were harvested at 3-week intervals, and the degree of obstruction of the inner cavity, the condition of epithelium, and the viability of chondrocytes were examined.


RESULTS
All of the isograft controls (BALB/c) and grafts implanted in the T cell-free recipients (BALB/c-nu) showed patent, lined epithelium and viable chondrocytes. All allografts tested showed total luminal occlusion by granulative tissue and inflammatory cells, and the epithelium was totally absent. Five of 11 drug-treated grafts were completely patent, although the epithelium was almost absent and the chondrocytes were substantially destroyed. However, when the chimerism was analyzed by flow cytometry analysis of the recipient T cells, approximately 90% of the donor cells were recognized.


CONCLUSIONS
Even by this pre-treatment-induced chimerism, a transplanted allogenic trachea was not completely preserved. The present results suggest that a non-allogenic response might have contributed to the rejection.
Suemitsu
Ryuichi
R
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. suemitsu@surg2.med.kyushu-u.ac.jp
Yoshino
Ichiro
I
Shoji
Fumihiro
F
Yamaguchi
Masafumi
M
Tomita
Yukihiro
Y
Maehara
Yoshihiko
Y
D000818:Animals; D000941:Antigens / Q000494:pharmacology*; D001989:Bronchiolitis Obliterans; D002066:Busulfan / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D004195:Disease Models, Animal; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D014019:Tissue Donors; D014132:Trachea / Q000473:pathology / Q000637:transplantation*; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D023001:Transplantation Tolerance; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous
D000941:Antigens; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D002066:Busulfan