受体MHC抗原诱导供体胚胎期免疫耐受应用于造血干细胞移植的研究

发布时间：2018-03-29 11:08

本文选题：MHC抗原　切入点：胚胎期　出处：《吉林大学》2009年硕士论文

【摘要】： 通过供体鼠胚胎期卵黄囊内途径接种受体鼠耐受原诱导免疫耐受,达到供体鼠造血干细胞对受体鼠的免疫耐受从而预防移植后GVHD的发生。本研究通过供体SD大鼠胚胎期卵黄囊内接种受体Wistar大鼠外周血单个核细胞(丰富表达MHC抗原);供体SD大鼠出生至性成熟后取其骨髓细胞移植给受体Wistar大鼠,移植前受体大鼠经Co608.0Gy照射清除其自身造血和免疫系统,骨髓移植后观测受体大鼠造血系统和免疫系统变化情况的实验方法,通过一下几个方面对结果进行检测:外周血白细胞计数和骨髓病理检测移植后造血恢复情况,采用PCR方法检测供体来源sry基因(Y染色体特异的性别决定基因)表达情况,取各脏器组织病理检测GVHD情况,采用皮肤移植及单相混合淋巴细胞反应方法检测受体免疫耐受情况。移植后发现:①实验组受体Wistar大鼠移植后105d成活率为85%,明显高于各对照组。②实验组受体Wistar大鼠照射移植后,白细胞计数经曲线变化回升至正常水平,骨髓病理示骨髓增生良好;PCR法可检测到供体SD大鼠来源的sry基因,说明骨髓移植后受体鼠体内重建了供体鼠来源的造血和免疫系统。③实验组病理检查仅见程度较轻的GVHD或无GVHD发生,而对照组可见明显的GVHD现象。④皮肤移植实验组受体Wistar大鼠对供体SD大鼠皮肤的移植排斥率较低,与第三无关供体比较有统计学差异;单相混合淋巴细胞反应显示实验组淋巴细胞呈低增值反应水平。综上可见通过供体SD大鼠胚胎期卵黄囊内接种耐受原诱导免疫耐受,一定程度上能够有效的预防造血干细胞移植后的GVHD的发生;供体SD大鼠胚胎期经卵黄囊内途径接种单个核细胞后,能够正常出生、存活,实验方法可行。
[Abstract]:Immunological tolerance was induced by inoculating the recipient mice with the immunoresistance in the yolk sac of donor mice at embryonic stage. To achieve the immune tolerance of donor hematopoietic stem cells to recipient mice and to prevent the occurrence of GVHD after transplantation, this study was conducted by inoculating peripheral blood mononuclear cells (PBMC) of recipient Wistar rats into the embryonic yolk sac of donor SD rats. Bone marrow cells were taken from donor SD rats from birth to sexual maturity and transplanted to recipient Wistar rats. The experimental method of removing autohematopoiesis and immune system by Co608.0Gy irradiation in recipient rats before transplantation and observing the changes of hematopoiesis and immune system in recipient rats after bone marrow transplantation. The results were examined in the following ways: peripheral blood leukocyte count and bone marrow pathological examination of hematopoietic recovery after transplantation, and the expression of donor-derived sry gene Y chromosome specific sex determinant gene by PCR method. GVHD was detected by pathological examination of every organ. Skin transplantation and monophasic mixed lymphocyte reaction were used to detect receptor immune tolerance. It was found that the survival rate of Wistar rats in the experimental group was 855d after transplantation, which was significantly higher than that of Wistar rats. The white blood cell count returned to normal level after curve change. Bone marrow pathology showed that sry gene from donor SD rats could be detected by bone marrow pathology. The results showed that the donor hematopoietic and immune system was reconstructed in the recipient mice after bone marrow transplantation. The pathological examination of the experimental group showed only mild GVHD or no GVHD. In the control group, there was obvious GVHD phenomenon. 4. The skin graft rejection rate of Wistar rats was lower than that of the third unrelated donor group, and there was a significant difference between the experimental group and the third unrelated donor group. The monophasic mixed lymphocyte reaction showed that the lymphocytes in the experimental group showed a low value-added response level, and the immunological tolerance was induced by inoculation of the donor SD rat embryo yolk sac into the yolk sac. To a certain extent, it can effectively prevent the occurrence of GVHD after hematopoietic stem cell transplantation. The donor SD rats can be born and survived after inoculating mononuclear cells through yolk sac in embryonic stage.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R392.4

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