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Attenuation of GVHD for allo-bone marrow transplantation recipient by fasL-fas pathway in an H-2 haplotype disparate mouse combination

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Summary

In order to explore a new special and effective way to prevent, graft versus, host disease (GVHD) after allogenic bone marrow transplantation (alle-BMT), the stem cell antigen-1 (Sea-1) carly hematopoietic cells (EHC) from BALB/c mouse (H-2d) were introduced with exogenous mouse Fas ligand (mFasL) cDNA gene by the retrevirus-mediated gene transfer and expanded for one week, and then they were co-cultured with the spleen mononuclear cells (SMNC) from BAC mouse (H-2d, h) 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.

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Correspondence to Liu Lingbo.

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LIU Lingbo, male, born in 1964. Associate Professor

This project was supported by a grant from National Natural Sciences Foundation of China (No. 39770767).

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Lingbo, L., Ping, Z., Zhongbo, H. et al. Attenuation of GVHD for allo-bone marrow transplantation recipient by fasL-fas pathway in an H-2 haplotype disparate mouse combination. Current Medical Science 24, 329–333 (2004). https://doi.org/10.1007/BF02861860

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  • DOI: https://doi.org/10.1007/BF02861860

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