https://scholars.lib.ntu.edu.tw/handle/123456789/193523
標題: | Induction of Tolerance toward Rat Cardiac Allografts by Treatment with Allochimeric Class I Mhc Antigen and Fty720 | 作者: | CHUEH, SHIH-CHIEH LING, TIAN WANG, MIN WANG, MOU-ER STEPKOWSKI STANISLAW M KAHAN BARRY D |
公開日期: | 1997 | 卷: | v.64 | 期: | n.10 | 起(迄)頁: | 1407-1414 | 來源出版物: | TRANSPLANTATION | 摘要: | Background. The combination of FTY720, a novel immunosuppressant, and allochimeric class I MHC proteins bearing donor-type amino acid(aa) epitope substitutions for host-type sequences induces tolerance of Wistar Furth (WF; RT1.A") hart allografts in ACI (RTI.A") recipients. Mehtods. Allochimeric α-1 h1 58-80-RTI.A" proteins were produced by substituting the allogeneic nucleotide sequence encoding 10 aa residues unique to the α1 helical (α1h) region of RTI/A1 Lewis (AsP58, Arg62, Glu 63, Gln65, Lys66, Gly69, Asn70, Asn73, Ser77, and Asn80) for native RTI.Aa residues. The RTI.Au and the RTI.A1 haplotypes share four of these aa ( Arg62, Glu63, Gln65, and Gly69). A baculovirus / Spodoptera frugiperda insect cell system was used to expres theα1h 1 58-80-RTI.Aa proteins. addition of a 3-day oral gavage of 0.05 mg/kg/day FTY720 to a single portal vein injection of 10μgα1 h 1 58-80-RTI.Aa protein induced permanent accentance of WF heart allografts in 16 of 26 ACI recipients (> 100 days); theα1h 1 58-80-RTI. Aa protein alone only modestly prolonged WF heart survival( 13.8±0.8 days). The same tolerogenic protocol did not prolong the survival of third-party Brown Norway (RTI.An) heart allografts (14.3±2.5 days) compared with FTY720 alone (14.0±2.3 days; NS ). Tolerant ACI recipients hearing primary WF heart allografts for more than 100 days accepted second WF hearts, but promptly rejected third-party Brown Norway heart grafts (9.3±1.5 days). The tolerant state was transferred to irradiated ACI rats (400 rad) with either purified T cells (4-10x10 7) or serum (1-2 ml) from tolerant hosts, and was not broken by daily intraperitoneal injections of interleukin-2 (1000 U/day; 7 days). Conclusions. The combination of allochimeric protein with FTY720 induces transplantation tolerance, a state that may be associated with the appearance of donor-specific regulatory factors. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/94226 |
顯示於: | 醫學系 |
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