TY - JOUR
T1 - Prolongation of Kidney Graft Survival by Cyclophosphamide-induced Tolerance in Rats
AU - Eto, Masatoshi
AU - Nishimura, Yousuke
AU - Matsuo, Kenichi
AU - Omoto, Kazuya
AU - Goto, Ken
AU - Kumuzawa, Joichi
AU - Nomoto, Kikuo
N1 - Funding Information:
This study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Health and Welfare, Japan.
PY - 1995/5
Y1 - 1995/5
N2 - In this study, we have extended a cyclophosphamide (CP)-induced tolerance system to kidney transplantation in rats to examine whether or not we can overcome fully allogeneic (major histocompatibility complex plus minor histocompatibility) antigen barriers in organ transplantation. In the recipient Lewis (LEW, RT11) rats that were primed intravenously with 4 X 108 spleen cells plus 2 X 108 bone marrow cells from Brown-Norway (BN, RT1n) rats and treated intraperitoneally with 100 mg./kg. of cyclophosphamide (CP) 2 days later, the survival of kidney allografts, but not skin allografts, from BN was prolonged as compared with that in the untreated LEW rats. Some of the kidney allografts survived for more than 100 days without further immunosuppressants. The tolerant state induced was tolerogen specific, and the suppression of tissue damage of the grafted kidney in such tolerant rats was also confirmed by the histopathological findings of the grafted kidney. These results indicate that considerable levels of tolerance can be induced, at least in organ transplantation, across fully allogeneic antigen barriers in rats by a CP-induced tolerance system. We believe that the present study is the first step in applying our CP-induced tolerance system using skin grafting in the murine model to clinical organ transplantation.
AB - In this study, we have extended a cyclophosphamide (CP)-induced tolerance system to kidney transplantation in rats to examine whether or not we can overcome fully allogeneic (major histocompatibility complex plus minor histocompatibility) antigen barriers in organ transplantation. In the recipient Lewis (LEW, RT11) rats that were primed intravenously with 4 X 108 spleen cells plus 2 X 108 bone marrow cells from Brown-Norway (BN, RT1n) rats and treated intraperitoneally with 100 mg./kg. of cyclophosphamide (CP) 2 days later, the survival of kidney allografts, but not skin allografts, from BN was prolonged as compared with that in the untreated LEW rats. Some of the kidney allografts survived for more than 100 days without further immunosuppressants. The tolerant state induced was tolerogen specific, and the suppression of tissue damage of the grafted kidney in such tolerant rats was also confirmed by the histopathological findings of the grafted kidney. These results indicate that considerable levels of tolerance can be induced, at least in organ transplantation, across fully allogeneic antigen barriers in rats by a CP-induced tolerance system. We believe that the present study is the first step in applying our CP-induced tolerance system using skin grafting in the murine model to clinical organ transplantation.
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U2 - 10.1016/S0022-5347(01)67506-2
DO - 10.1016/S0022-5347(01)67506-2
M3 - Article
C2 - 7715012
AN - SCOPUS:0028924473
VL - 153
SP - 1693
EP - 1696
JO - Investigative Urology
JF - Investigative Urology
SN - 0022-5347
IS - 5
ER -