Chimerism is required for neonatal transplantation tolerance
Zhiwei Quan, 明亮, 全志伟, Zheng Pei-guo, Shuijun Zhang, Liang Ming, 郑配国, 张水军
Abstract
Zhiwei Quan, 明亮, 全志伟, Zheng Pei-guo, Shuijun Zhang, Liang Ming, 郑配国, 张水军
Abstract
Objective To investigate the mechanisms of neonatal transplantation tolerance,especially the role of immature immune system and chimerism in tolerance.Methods F1 ( or GFP-F1 ) mice were bred by crossing male C57BL/6 (or GPF transgenic C57BL/6) and female BALB/c mice. Within 24 h,newborn C57BL/6 mice were inoculated with different doses of splenocytes from F1 or GFP-F1 mice,irradiated spleen cells were used as control.Six weeks later,the mice were subjected to F1 skin grafting,and mixed-lymphocyte reaction was performed to determine their tolerance.Flow analysis was used to detect chimerism.Results Living F1 spleen cells could induce chimerism and neonatal transplantation tolerance,but irradiated cells not.The chimerism in long-term tolerant mice is higher than that in chronic rejected mice,with 6.48% ±4.02% vs 1.57% ±0.89%,the difference is significant in statistical analysis.The degree of neonatal transplantation tolerance is determined by the dosage of donor cells,the mice induced with 3 × 107 F1 spleen cells have 80% long-term tolerance,but the dose of0.7×107 F1 spleen cells could only prolong allografts survival.Conclusion Neonatal transplantation tolerance is dependent on chimerism,the chimerism of donor cells leads to clonal deletion of alloreactive T cells. Key words: Neonatal transplantation tolerance; Clonal deletion; Chimerism; Alloreactive T cells
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Objective To investigate the mechanisms of neonatal transplantation tolerance,especially the role of immature immune system and chimerism in tolerance.Methods F1 ( or GFP-F1 ) mice were bred by crossing male C57BL/6 (or GPF transgenic C57BL/6) and female BALB/c mice. Within 24 h,newborn C57BL/6 mice were inoculated with different doses of splenocytes from F1 or GFP-F1 mice,irradiated spleen cells were used as control.Six weeks later,the mice were subjected to F1 skin grafting,and mixed-lymphocyte reaction was performed to determine their tolerance.Flow analysis was used to detect chimerism.Results Living F1 spleen cells could induce chimerism and neonatal transplantation tolerance,but irradiated cells not.The chimerism in long-term tolerant mice is higher than that in chronic rejected mice,with 6.48% ±4.02% vs 1.57% ±0.89%,the difference is significant in statistical analysis.The degree of neonatal transplantation tolerance is determined by the dosage of donor cells,the mice induced with 3 × 107 F1 spleen cells have 80% long-term tolerance,but the dose of0.7×107 F1 spleen cells could only prolong allografts survival.Conclusion Neonatal transplantation tolerance is dependent on chimerism,the chimerism of donor cells leads to clonal deletion of alloreactive T cells. Key words: Neonatal transplantation tolerance; Clonal deletion; Chimerism; Alloreactive T cells
Key concepts: Splenocyte, Spleen, Immune tolerance, Transplantation, Chimera (genetics), Immunology, Mixed lymphocyte reaction, Biology