抗CD45RB抗体在诱导免疫耐受中对T淋巴细胞亚群的作用

发布时间：2018-03-11 07:21

本文选题：免疫耐受　切入点：CD45RB抗体　出处：《暨南大学》2010年硕士论文　论文类型：学位论文

【摘要】： 目的：研究抗CD45RB抗体在诱导免疫耐受中对不同T淋巴细胞亚群的影响,以阐明T细胞亚群在抗CD45RB抗体诱导的免疫耐受中可能发挥的作用机制。方法：将T淋巴细胞与ConA或抗CD45RB抗体共培养72小时,检测淋巴细胞增殖被抑制能力。取BALB/c鼠脾细胞作为刺激细胞,与C57BL/6鼠T淋巴细胞或抗CD45RB抗体共培养72小时后收集混合细胞和培养上清。建立小鼠心脏移植模型,观察抗CD45RB抗体对移植物生存期的影响。在移植术后第0、1、3、5、7天时取外周血、脾脏组织和移植心脏。流式细胞术分析混合细胞和外周血中Th1 (CD3+CD8"IFN-y+)、Th2 (CD3+CD8'IL-4+)、Treg (CD4+CD25+CD127-)、Ts(CD8+CD28")、Tm(CD4+CD62L-CD44hi)变化；ELISA法检测培养上清和血清中IL-2、IL-4、IL-10、IFN-y含量；Real-Time PCR法检测混合细胞和脾脏组织Foxp3 mRNA;病理学观察移植心脏组织学变化。结果：抗CD45RB抗体显着延长移植物存活时间,对ConA刺激引起的T淋巴细胞增殖具有明显的抑制能力。与对照组相比,抗CD45RB抗体能明显上调混合细胞和外周血中Th2细胞、Treg细胞和TS细胞,下调Th1细胞和Tm细胞；可使细胞因子IL-2和IFN-γ的水平降低,IL-4和IL-10的含量升高；增加Foxp3 mRNA的表达量。病理学显示对照组移植心脏出现典型细胞免疫性损伤病理改变,而实验组中几乎无炎性细胞浸润现象。结论：抗CD45RB抗体能显着明显延长移植物存活时间,其诱导免疫耐受可能与上调Th2细胞、Treg细胞和TS细胞,下调Th1细胞和Tm细胞,增加Foxp3 mRNA表达量有关。
[Abstract]:Aim: to study the effect of anti CD45RB antibody on different T lymphocyte subsets in inducing immune tolerance, and to elucidate the role of T cell subsets in the immune tolerance induced by anti CD45RB antibody. Methods: t lymphocytes were co-cultured with ConA or anti CD45RB antibody for 72 hours to detect the ability of inhibiting lymphocyte proliferation. Spleen cells of BALB/c mice were used as stimulators. Mixed cells and supernatants were collected and cultured after 72 hours co-culture with C57BL / 6 T lymphocytes or anti CD45RB antibody. The mouse heart transplantation model was established to observe the effect of anti CD45RB antibody on graft survival. Splenic tissue and heart grafts. Flow cytometry analysis of the changes of Th1 T cell line CD3 CD8 "IFN-y Th _ 2 T _ 3 CD8'IL-4" T _ 4 CD25 CD _ (127-T) CD _ (8) CD28 "T _ m T _ m CD _ 4 ~ + CD _ 62L-CD44hi. Elisa for the detection of IL-2IL-4IL-10IL-10IFN-y in culture supernatant and serum; Real-Time PCR method) for detection of Foxp3 in mixed and splenic tissues. MRNAs; histopathological changes of transplanted heart. Results: anti CD45RB antibody significantly prolonged the survival time of grafts and significantly inhibited the proliferation of T lymphocytes stimulated by ConA. Anti CD45RB antibody could significantly up-regulate Th2 cells, Treg cells and TS cells, down-regulate Th1 cells and TM cells, decrease the levels of cytokines IL-2 and IFN- 纬 and increase the contents of IL-4 and IL-10 in mixed cells and peripheral blood cells. The expression of Foxp3 mRNA was increased and the pathological changes of typical cellular immunological injury were observed in the control group, but there were almost no inflammatory cell infiltration in the experimental group. Conclusion: anti CD45RB antibody can significantly prolong the survival time of grafts and its induction of immune tolerance may be related to up-regulating the expression of Foxp3 mRNA in Th2 cells and TS cells down-regulating Th1 cells and TM cells and increasing the expression of Foxp3 mRNA.
【学位授予单位】：暨南大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R392

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