Long-term observation after simultaneous lung and intra-bone marrow-bone marrow transplantation.
BACKGROUND
Although lung transplantation is now an established treatment for end-stage lung diseases, allogeneic transplantation of parenchymal organs requires immunosuppressive therapy to prevent rejection. It has been reported that bone marrow transplantation (BMT) induces specific tolerance to donor organs. We have recently discovered a new method for BMT, which is called intra-bone marrow (IBM) BMT, in which bone marrow cells (BMCs) are injected directly into the bone marrow cavity. We demonstrate that IBM-BMT can be used to induce tolerance even in simultaneous lung transplantations in rats without administering any immunosuppressants.


METHODS
Allogeneic lung transplantation was carried out from Brown Norway to Lewis rats. Simultaneously, IBM-BMT was carried out.


RESULTS
Transplantation of nonirradiated lung or nontreated BMCs (T cell-containing BMCs) induced graft vs host disease. Therefore, the donor lung was irradiated, and T cells in the BMCs were depleted by anti-CD4, anti-CD5, and anti-CD8 antibodies plus anti-mouse antibody-coated magnetic beads. Lung allografts with conventional (intravenous) BMT failed to induce tolerance. However, the recipients treated with lung allografts plus IBM-BMT, which showed either mixed chimerism or full chimerism of hematopoietic cells, did not show symptoms of graft rejection or graft vs host disease, even without the use of immunosuppressants.


CONCLUSIONS
These results suggest that simultaneous lung transplantation and IBM-BMT (but not conventional BMT) is effective in inducing persistent tolerance without the use of immunosuppressants.
Kaneda
Hiroyuki
H
First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan.
Adachi
Yasushi
Y
Saito
Yukihito
Y
Ikebukuro
Kazuya
K
Machida
Hirohisa
H
Suzuki
Yasuhiro
Y
Minamino
Keizo
K
Zhang
Yuming
Y
Iwasaki
Masayoshi
M
Nakano
Keiji
K
Koike
Yasushi
Y
Wang
Jianfeng
J
Imamura
Hiroji
H
Ikehara
Susumu
S
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000379:methods; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D008168:Lung / Q000502:physiology; D016040:Lung Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014183:Transplantation, Heterologous