SUMMARY The induction of transplantation tolerance and the improvement of immune reconstitution after allogeneic bone marrow transplantation are the main research fields in the clinic organ transplantation and transpl...SUMMARY The induction of transplantation tolerance and the improvement of immune reconstitution after allogeneic bone marrow transplantation are the main research fields in the clinic organ transplantation and transplantation immunology.Over the past 5 years serial studies have been performed in our lab to induce robust transplantation tolerance by using combinated strategies and improve the immune reconstitution of mice following allogeneic bone marrow transplantation by using gene-engineered bone marrow stromal cells.The results are encouraging.(1)The long-term survival of allografts was received by blockade of both CD28/B7 and CD40/CD40L or CD28/B7 and OX40/OX40L costimulating signals.In the case of blockade of both CD28/B7 and OX40/OX40L,the islet allograft survival was over 150 days compared to the control 14 days.(2)The CTLA4Ig-FasL fusion molecule expressed by adenoviral vector containing CTLA4Ig-FasL gene can prevent the autoimmune diabetes of mice and significantly prolong the survival time of cardiac allografts in rats,indicating that Fas-FasL-mediated apoptosis is able to enhance CTLA4Ig-induced transplantation tolerance.(3)In the time-window of peripheral tolerance induced by various methods,the systemic infusion of donor bone marrow cells and spleen cells obtained stable allogeneic mixed chimerisms and robust transplantation tolerance.In the case of CTLA4Ig-FasL treatment combinated with donor bone marrow cells more than 20% donor-origin blood cells chimerism,and more than 200 days prolonged skin allograft survival were obtained or received.(4)The murine bone marrow stromal cell line QXMSC1 transfected with IL-6 gene or IL-2+IL-3 genes significantly improved the immune reconstitution of mice following allogeneic bone marrow transplantation.Furthermore,It was observed that the mesenchymal stem cells transfected with IL-7 gene suppressed 90% of GVHD and expressed antileukemic effect,while accelerating immune reconstitution in mice following allogeneic bone marrow transplantation,which might be valuable in the clinic setting.展开更多
目的:观察脑缺血环境下胚胎干细胞源性树突状细胞(es DCs)能否诱导同源性神经前体细胞(NPCs)的移植耐受。方法:分别自129/svj p CX-e GFP ES-D3诱生NPCs及129/svj ES-D3诱生es DCs。线栓法制作MCAo模型SD大鼠并相应分为预处理组及对照组...目的:观察脑缺血环境下胚胎干细胞源性树突状细胞(es DCs)能否诱导同源性神经前体细胞(NPCs)的移植耐受。方法:分别自129/svj p CX-e GFP ES-D3诱生NPCs及129/svj ES-D3诱生es DCs。线栓法制作MCAo模型SD大鼠并相应分为预处理组及对照组,术后1周预处理组经尾静脉注射es DCs而对照组注射PBS,两组动物在预处理1周后侧脑室注射NPCs,2周后(MCAo术后4周)免疫组化观察纹状区CD4+、CD8+、ED1+细胞的分布差异,MTT法观察颈部淋巴细胞增殖性(PI),逆转录PCR(RT-PCR)半定量局部IL-10、IFN-γmRNA表达差异,荧光显微镜观察GFP标记NPCs海马存活率。结果:预处理组大鼠,CD4+细胞浸润显著低于对照组(134.7±36.2 vs 198.8±59.6,P<0.05),NPCs存活率显著高于对照组(P<0.05),但预处理组对ED1+(298.8±75.9 vs 302.2±88.5)、CD8+(145.8±45.4 vs 134.3±39.0)细胞浸润、局部细胞因子mRNA IFN-γ(1.697±0.273 vs 1.829±0.250)、IL-10(1.147±0.260 vs 1.264±0.119)及外周淋巴细胞增长率(PI,1.245±0.211 vs1.331±0.235)无明显影响。结论:es DC可能通过降低局部CD4+细胞反应诱导针对同源性NPCs免疫耐受,尚无确切证据表明细胞因子途径参与该过程,确切的机理尚需更深入研究。展开更多
文摘SUMMARY The induction of transplantation tolerance and the improvement of immune reconstitution after allogeneic bone marrow transplantation are the main research fields in the clinic organ transplantation and transplantation immunology.Over the past 5 years serial studies have been performed in our lab to induce robust transplantation tolerance by using combinated strategies and improve the immune reconstitution of mice following allogeneic bone marrow transplantation by using gene-engineered bone marrow stromal cells.The results are encouraging.(1)The long-term survival of allografts was received by blockade of both CD28/B7 and CD40/CD40L or CD28/B7 and OX40/OX40L costimulating signals.In the case of blockade of both CD28/B7 and OX40/OX40L,the islet allograft survival was over 150 days compared to the control 14 days.(2)The CTLA4Ig-FasL fusion molecule expressed by adenoviral vector containing CTLA4Ig-FasL gene can prevent the autoimmune diabetes of mice and significantly prolong the survival time of cardiac allografts in rats,indicating that Fas-FasL-mediated apoptosis is able to enhance CTLA4Ig-induced transplantation tolerance.(3)In the time-window of peripheral tolerance induced by various methods,the systemic infusion of donor bone marrow cells and spleen cells obtained stable allogeneic mixed chimerisms and robust transplantation tolerance.In the case of CTLA4Ig-FasL treatment combinated with donor bone marrow cells more than 20% donor-origin blood cells chimerism,and more than 200 days prolonged skin allograft survival were obtained or received.(4)The murine bone marrow stromal cell line QXMSC1 transfected with IL-6 gene or IL-2+IL-3 genes significantly improved the immune reconstitution of mice following allogeneic bone marrow transplantation.Furthermore,It was observed that the mesenchymal stem cells transfected with IL-7 gene suppressed 90% of GVHD and expressed antileukemic effect,while accelerating immune reconstitution in mice following allogeneic bone marrow transplantation,which might be valuable in the clinic setting.
文摘目的:观察脑缺血环境下胚胎干细胞源性树突状细胞(es DCs)能否诱导同源性神经前体细胞(NPCs)的移植耐受。方法:分别自129/svj p CX-e GFP ES-D3诱生NPCs及129/svj ES-D3诱生es DCs。线栓法制作MCAo模型SD大鼠并相应分为预处理组及对照组,术后1周预处理组经尾静脉注射es DCs而对照组注射PBS,两组动物在预处理1周后侧脑室注射NPCs,2周后(MCAo术后4周)免疫组化观察纹状区CD4+、CD8+、ED1+细胞的分布差异,MTT法观察颈部淋巴细胞增殖性(PI),逆转录PCR(RT-PCR)半定量局部IL-10、IFN-γmRNA表达差异,荧光显微镜观察GFP标记NPCs海马存活率。结果:预处理组大鼠,CD4+细胞浸润显著低于对照组(134.7±36.2 vs 198.8±59.6,P<0.05),NPCs存活率显著高于对照组(P<0.05),但预处理组对ED1+(298.8±75.9 vs 302.2±88.5)、CD8+(145.8±45.4 vs 134.3±39.0)细胞浸润、局部细胞因子mRNA IFN-γ(1.697±0.273 vs 1.829±0.250)、IL-10(1.147±0.260 vs 1.264±0.119)及外周淋巴细胞增长率(PI,1.245±0.211 vs1.331±0.235)无明显影响。结论:es DC可能通过降低局部CD4+细胞反应诱导针对同源性NPCs免疫耐受,尚无确切证据表明细胞因子途径参与该过程,确切的机理尚需更深入研究。
