Attenuation of GVHD for allo-bone marrow transplantation recipient by FasL-Fas pathway in an H-2 haplotype disparate mouse combination.
- Author:
Lingbo LIU
1
;
Ping ZOU
;
Zhongbo HU
;
Zhaodong ZHONG
;
Juan XIAO
;
Rong GUO
;
Zhiliang XU
Author Information
1. Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. liulinbo@medmail.com.cn
- Publication Type:Journal Article
- MeSH:
Animals;
Bone Marrow Transplantation;
Fas Ligand Protein;
Female;
Graft vs Host Disease;
immunology;
therapy;
H-2 Antigens;
genetics;
Haplotypes;
Hematopoietic Stem Cells;
cytology;
immunology;
Membrane Glycoproteins;
immunology;
Mice;
Mice, Inbred BALB C;
Mice, Inbred C57BL;
Rats;
Rats, Wistar;
Signal Transduction;
Spleen;
cytology;
immunology;
T-Lymphocytes;
immunology;
Transfection;
fas Receptor;
immunology
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2004;24(4):329-333
- CountryChina
- Language:English
-
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.