title: Attenuation of GVHD for allo-bone marrow transplantation recipient by FasL-Fas pathway in an H-2 haplotype disparate mouse combination.
abstract: In order to explore a new special and effective way to prevent graft versus host disease (GVHD) after allogenic bone marrow transplantation (allo-BMT), the stem cell antigen-1 (Sca-1) + early hematopoietic cells (EHC) from BALB/c mouse (H-2d) were introduced with exogenous mouse Fas ligand (mFasL) cDNA gene by the retrovirus-mediated gene transfer and expanded for one week, and then they were co-cultured with the spleen mononuclear cells (SMNC) from BAC mouse (H-2dxb) as one way mixed lymphocyte reaction (OWMLR). The cytotoxicity of treated BAC mouse SMNC against Na2 51CrO4 labeling SMNC from BALB/c mouse was observed. The bone marrow mononuclear cells (BMMNC) from BAC mouse treated by the above methods were transplanted into lethally-irradiated congenic BALB/c mice to observe the occurrence of GVHD. The results showed that the SMNC from BAC mouse after OWMLR with exogenous mFasL cDNA gene-transduced hematopoietic cells (HC) from BALB/c mouse in a ratio of 1 to 5 exhibited an obvious inhibition of the cytotoxicity against the BALB/c mouse spleen cells at different effector/target ratios as compared to the control group (P<0.01). The grade I GVHD or no GVHD and the 80% survival rate at day 60 post-BMT were observed in the BALB/c mouse receiving BAC mouse BMMNC treated with similar way, while the grade II - III GVHD and the 20% survival rate were noted in the control group (P<0.01). It is suggested that the attenuation of GVHD in allo-BMT recipient could be successfully achieved through FasL-Fas pathway in an H-2 haplotype disparate mouse combination.
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. liulinbo@medmail.com.cn
authors.forename: Lingbo
authors.initials: L
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Zou
authors.forename: Zhongbo
authors.initials: Z
authors.lastname: Hu
authors.forename: Zhaodong
authors.initials: Z
authors.lastname: Zhong
authors.forename: Juan
authors.initials: J
authors.lastname: Xiao
authors.forename: Rong
authors.initials: R
authors.lastname: Guo
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D053222:Fas Ligand Protein; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000628:therapy*; D006183:H-2 Antigens / Q000235:genetics; D006239:Haplotypes; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D019014:fas Receptor / Q000276:immunology*
chemical_list: D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; C505662:Faslg protein, rat; D006183:H-2 Antigens; D008562:Membrane Glycoproteins; D019014:fas Receptor