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Status of autoimmune diabetes 20-year after generation of BDC2.5-TCR transgenic non-obese diabetic mouse
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作者 Lourdes Ramirez Abdel Rahim A Hamad 《World Journal of Diabetes》 SCIE CAS 2013年第4期88-91,共4页
Type 1 diabetes(T1D) is an autoimmune disease that results from the destruction of insulin-producing cells by autoreactive T cells,leading to lifelong dependency on insulin therapy and increased risk of long-term card... Type 1 diabetes(T1D) is an autoimmune disease that results from the destruction of insulin-producing cells by autoreactive T cells,leading to lifelong dependency on insulin therapy and increased risk of long-term cardiovascular complications.Here we take the opportunity of the 20thanniversary of the generation of the BDC2.5 TCR transgenic non-obese diabetic(NOD) mouse model,to provide a brief overview of the significant progress that has been made in understanding the role of T cells in the disease pathogenesis period.This included development of hundreds of reagents that block or even reverse new-onset disease by directly or indirectly controlling T cells.We also reflect on the sobering fact that none of these strategies has shown significant efficacy in clinical trials and discuss potential reasons hindering translation of the preclinical findings into successful therapeutic strategies and potential ways forward. 展开更多
关键词 AUtOIMMUNE diabetes IMMUNOtHERAPY t cells bdc2.5 t cells Anti-CD3 IMMUNOSUPPRESSION
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PM2.5对哮喘大鼠IL-17/IL-23炎症介质的影响及人参皂苷Rg1干预研究 被引量:11
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作者 周亚兵 蒋思韵 +1 位作者 王利维 华丽 《世界中医药》 CAS 2021年第10期1520-1525,共6页
目的:基于气道IL-17/IL-23炎症介质轴,探讨人参皂苷Rg1对PM2.5哮喘大鼠肺损伤保护机制。方法:采集并分离交通相关大气细颗粒物PM2.5,利用卵白蛋白致敏和激发建立幼龄哮喘大鼠模型,再给予PM2.5气管滴注建立PM2.5哮喘肺损伤模型,采用酶联... 目的:基于气道IL-17/IL-23炎症介质轴,探讨人参皂苷Rg1对PM2.5哮喘大鼠肺损伤保护机制。方法:采集并分离交通相关大气细颗粒物PM2.5,利用卵白蛋白致敏和激发建立幼龄哮喘大鼠模型,再给予PM2.5气管滴注建立PM2.5哮喘肺损伤模型,采用酶联免疫吸附试验(ELISA)法测定血清和肺泡灌洗液IL-17a、IL-6、IL-23、TGF-β_(1)含量,RT-PCR检测RORγt mRNA表达,并行肺组织病理和电镜分析。结果:成功建立PM2.5气管滴注哮喘大鼠模型;哮喘大鼠模型血清和肺泡灌洗液IL-17a、IL-6、IL-23、TGF-β_(1)表达量增大(P<0.01),肺组织RORγt mRNA表达量增加(P<0.01);经PM2.5气管滴注后,模型组大鼠血清和肺泡灌洗液IL-17a、IL-6、IL-23、TGF-β_(1)含量进一步增加,RORγt mRNA表达量进一步上升(P<0.01);经皂苷Rg1干预后,呈现剂量依赖性下调血清和肺泡灌洗液IL-17a、IL-6、IL-23、TGF-β_(1)水平,下调RORγt mRNA表达量。结论:人参皂苷Rg1呈剂量依赖性改善PM2.5致哮喘大鼠肺气道炎症反应、改善肺损伤。 展开更多
关键词 哮喘 大气颗粒物2.5 辅助性t细胞17 白细胞介素-17 白细胞介素-23 维A酸相关孤儿受体γt 人参皂苷RG1
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多房棘球绦虫重组Bb—EmⅡ/3-Em14—3—3疫苗诱导BALB/c小鼠T淋巴细胞亚群变化的研究 被引量:5
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作者 杨梅 李文桂 刘兴超 《中华地方病学杂志》 CAS CSCD 北大核心 2016年第9期629-632,共4页
目的探讨多房棘球绦虫(Em)重组Bb-EmⅡ/3-Eml4.3.3疫苗免疫和Em原头节攻击后小鼠脾CD4+和CD8+T淋巴细胞亚群的变化。方法用重组Bb-EmⅡ/3-Em14.3.3疫苗分别通过皮下注射、肌肉注射、鼻腔黏膜接种以及口服接种免疫BALB/c小鼠... 目的探讨多房棘球绦虫(Em)重组Bb-EmⅡ/3-Eml4.3.3疫苗免疫和Em原头节攻击后小鼠脾CD4+和CD8+T淋巴细胞亚群的变化。方法用重组Bb-EmⅡ/3-Em14.3.3疫苗分别通过皮下注射、肌肉注射、鼻腔黏膜接种以及口服接种免疫BALB/c小鼠,双歧杆菌(Bb)液和磷酸盐缓冲液(PBS)为对照,12周后,用50个Em原头蚴腹腔注射进行攻击,攻击感染18周剖杀小鼠,检获泡球蚴组织,称取重量,计算减蚴率;分离脾细胞,流式细胞仪检测脾CD4+和CD8+T淋巴细胞亚群的百分比。结果疫苗免疫组(皮下注射、肌肉注射、鼻腔黏膜接种、口服接种)小鼠检获泡球蚴重量[(0.77±0.52)、(0.87±0.60)、(2.17±0.50)、(3.06±0.15)g]均明显低于PBS对照组[(3.54±0.32)g.P〈0.05或〈0.01]。疫苗免疫组(皮下注射、肌肉注射、鼻腔黏膜接种、口服接种)小鼠脾CD4+T细胞亚群[(28.2±2.5)%、(25.0±2.7)%、(24.0±1.3)%、(23.0±1.8)%]显著高于PBS对照组[(16.1±2.2)%,P均〈0.01];各疫苗免疫组小鼠CD8+T细胞亚群水平均轻微升高,但组间比较差异无统计学意义(F=1.36,P〉0.05)。皮下注射组小鼠CD4+T细胞亚群高于肌肉注射组、鼻腔黏膜接种组和口服接种组(P均〈0.05)。结论CD4+T细胞亚群在Em重组Bb-EmⅡ/3-Em14-3-3疫苗诱导的小鼠抗Em原头节攻击感染的保护性免疫机制中起关键作用,疫苗皮下注射是一种较好的免疫途径。 展开更多
关键词 多房棘球绦虫 重组Bb-EmⅡ/3-Em14-3-3疫苗 t淋巴细胞亚群
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I L- 15 trans-presentation regulates homeostasis of CD4^+ T lymphocytes
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作者 Xi-Lin Chen Diwakar Bobbala +3 位作者 Yuneivy Cepero Donates Marian Mayhue Subburaj Ilangumaran Sheela Ramanathan 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2014年第4期387-395,共9页
Interleukin-15 (IL-15) is essential for the survival of memory CD8^+ and CD4^+ T cell subsets, and natural killer and natural killer T cells. Here, we describe a hitherto unreported role of IL-15 in regulating hom... Interleukin-15 (IL-15) is essential for the survival of memory CD8^+ and CD4^+ T cell subsets, and natural killer and natural killer T cells. Here, we describe a hitherto unreported role of IL-15 in regulating homoeostasis of naive CD4^+ T cells. Adoptive transfer of splenocytes from non-obese diabetic (NOD) mice results in increased homeostatic expansion of T cells in lymphopenic NOD.scid.II15^-/- mice when compared to NOD.scid recipients. The increased accumulation of CD4^+ T cells is also observed in NOD.II15^-/- mice, indicating that IL-15-dependent regulation also occurs in the absence of lymphopenia. NOD.scid mice lacking the I L- 15Ra chain, but not those lacking the common gamma chain, also show increased accumulation of CD4^+ T cells. These findings indicate that the IL-15-mediated regulation occurs directly on CD4^+ T cells and requires trans-presentation of IL-15. CD4^+ T cells expanding in the absence of IL-15 signaling do not acquire the characteristics of classical regulatory T cells. Rather, CD4^+ T cells expanding in the absence of IL-15 show impaired antigen-induced activation and IFN-7 production. Based on these findings, we propose that the IL-15-dependent regulation of the naive CD4^+ T-cell compartment may represent an additional layer of control to thwart potentially autoreactive cells that escape central tolerance, while permitting the expansion of memory T cells. 展开更多
关键词 bdc2.5 CD4^+ t cells HOMEOStASIS IL-15 NOD mouse
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