留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

抗体诱导的移植免疫耐受依赖于B细胞来源的TGF-β的调节

赵高平 杨卯竹 李姝蓉 魏玲玲 邓绍平

赵高平, 杨卯竹, 李姝蓉, 等. 抗体诱导的移植免疫耐受依赖于B细胞来源的TGF-β的调节[J]. 器官移植, 2016, 7(3): 171-176. doi: 10.3969/j.issn.1674-7445.2016.03.002
引用本文: 赵高平, 杨卯竹, 李姝蓉, 等. 抗体诱导的移植免疫耐受依赖于B细胞来源的TGF-β的调节[J]. 器官移植, 2016, 7(3): 171-176. doi: 10.3969/j.issn.1674-7445.2016.03.002
Zhao Gaoping, Yang Maozhu, Li Shurong, et al. Effect of B cell-derived TGF-β on regulating antibody-induced immune tolerance after transplantation[J]. ORGAN TRANSPLANTATION, 2016, 7(3): 171-176. doi: 10.3969/j.issn.1674-7445.2016.03.002
Citation: Zhao Gaoping, Yang Maozhu, Li Shurong, et al. Effect of B cell-derived TGF-β on regulating antibody-induced immune tolerance after transplantation[J]. ORGAN TRANSPLANTATION, 2016, 7(3): 171-176. doi: 10.3969/j.issn.1674-7445.2016.03.002

抗体诱导的移植免疫耐受依赖于B细胞来源的TGF-β的调节

doi: 10.3969/j.issn.1674-7445.2016.03.002
基金项目: 

国家自然科学基金 81172832

国家自然科学基金 81571565

四川省杰出青年基金 2013JQ0020

四川省青年科技创新团队专项计划 2014TD0010

四川省卫生和计划生育委员会课题 110190

详细信息
    通讯作者:

    赵高平,Email:gzhao@uestc.edu.cn

    邓绍平,Email: dengshaoping@uestc.edu.cn

  • 中图分类号: R617, R392.3, R587.1

Effect of B cell-derived TGF-β on regulating antibody-induced immune tolerance after transplantation

More Information
  • 摘要:   目的   研究抗CD45RB抗体或联合抗Tim-1抗体诱导的移植免疫耐受中转化生长因子(TGF)-β的调节作用。  方法  建立小鼠同种异体心脏移植以及胰岛移植模型,前者用抗CD45RB抗体和(或)抗TGF-β抗体治疗,后者用抗CD45RB抗体联合抗Tim-1抗体治疗并加用或不用抗TGF-β抗体,观察移植物长期存活时间。分离胰岛移植物长期耐受的受体B细胞,过继输注至胰岛细胞移植模型小鼠体内,经抗TGF-β抗体治疗后观察移植胰岛的存活情况。在体外将经双抗体治疗14 d的移植有胰岛细胞的受体B细胞与脂多糖(LPS)混合刺激培养过夜,采用流式细胞仪检测CD19+LAP+细胞的比例。  结果  抗CD45RB抗体治疗后有6/9的同种异体小鼠心脏长期存活,但若加用抗TGF-β抗体治疗则所有移植心脏均被排斥。在小鼠胰岛细胞移植模型中,抗CD45RB抗体联合抗Tim-1抗体治疗后有90%移植物长期耐受,但加用抗TGF-β抗体后则无1例移植物长期存活。B细胞输注治疗后,8/9的胰岛移植物不被排斥,而加用抗TGF-β抗体后则移植物很快被排斥。B细胞体外刺激培养,流式细胞术检测显示CD19+LAP+细胞在B细胞中的比例显著增高(P < 0.0001)。  结论  抗CD45RB抗体或联合抗Tim-1抗体诱导的移植免疫耐受需要TGF-β,其可能受调节性B细胞的调节。

     

  • 图  1  各组心脏移植模型小鼠的生存曲线

    Figure  1.  Survival curves of mice after cardiac transplantation among each group

    图  2  3组B细胞中CD19+LAP+细胞比例的比较

    注:aP < 0.0001

    Figure  2.  Comparison of rates of CD19+LAP+ cells in B cells of 3 groups

  • [1] 宋继勇, 石炳毅.调节性B细胞与器官移植[J].器官移植, 2015, 6(3):197-200. http://www.organtranspl.com/browse/detail/qkid/72/id/86.html

    Song JY, Shi BY. Regulate B cell and organ transplantation[J]. Organ Transplant, 2015, 6(3):197-200. http://www.organtranspl.com/browse/detail/qkid/72/id/86.html
    [2] Zhao G, Moore DJ, Lee KM, et al. An unexpected counter-regulatory role of IL-10 in B-lymphocyte-mediated transplantation tolerance [J]. Am J Transplant, 2010, 10(4):796-801. doi: 10.1111/ajt.2010.10.issue-4
    [3] Ono K, Lindsey ES. Improved technique of heart transplantation in rats [J]. J Thorac Cardiovasc Surg, 1969, 57(2):225-229. http://cn.bing.com/academic/profile?id=2095316325&encoded=0&v=paper_preview&mkt=zh-cn
    [4] Guo Y, Zhang X, Qin M, et al. Changes in peripheral CD19(+)Foxp3(+) and CD19(+)TGFβ(+) regulatory B cell populations in rheumatoid arthritis patients with interstitial lung disease [J]. J Thorac Dis, 2015, 7(3):471-477. https://www.researchgate.net/publication/275661403_Changes_in_peripheral_CD19Foxp3_and_CD19TGFb_regulatory_B_cell_populations_in_rheumatoid_arthritis_patients_with_interstitial_lung_disease
    [5] Nouёl A, Pochard P, Simon Q, et al. B-Cells induce regulatory T cells through TGF-β/IDO production in a CTLA-4 dependent manner [J]. J Autoimmun, 2015, 59:53-60. doi: 10.1016/j.jaut.2015.02.004
    [6] Joly MS, Martin RP, Mitra-Kaushik S, et al. Transient low-dose methotrexate generates B regulatory cells that mediate antigen-specific tolerance to alglucosidase alfa [J]. J Immunol, 2014, 193(8):3947-3958. doi: 10.4049/jimmunol.1303326
    [7] Braza F, Chesne J, Castagnet S, et al. Regulatory functions of B cells in allergic diseases [J]. Allergy, 2014, 69(11):1454-1463. doi: 10.1111/all.2014.69.issue-11
    [8] Clark MC, Baum LG. T cells modulate glycans on CD43 and CD45 during development and activation, signal regulation, and survival[J]. Ann N Y Acad Sci, 2012, 1253:58-67. doi: 10.1111/j.1749-6632.2011.06304.x
    [9] McCarron MJ, Marie JC. TGF-β prevents T follicular helper cell accumulation and B cell autoreactivity [J]. J Clin Invest. 2014, 124(10):4375-4386. doi: 10.1172/JCI76179
    [10] Kumar P, Naumann U, Aigner L, et al. Impaired TGF-β induced growth inhibition contributes to the increased proliferation rate of neural stem cells harboring mutant p53 [J]. Am J Cancer Res, 2015, 5(11):3436-3445. http://www.pubfacts.com/detail/26807323/Impaired-TGF-induced-growth-inhibition-contributes-to-the-increased-proliferation-rate-of-neural-ste
    [11] Shull MM, Ormsby I, Kier AB, et al. Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease [J]. Nature, 1992, 359(6397):693-699. doi: 10.1038/359693a0
    [12] Gros MJ, Naquet P, Guinamard RR. Cell intrinsic TGF-beta 1 regulation of B cells [J]. J Immunol, 2008, 180(12):8153-8158. doi: 10.4049/jimmunol.180.12.8153
    [13] Lee KM, Kim JI, Stott R, et al. Anti-CD45RB/anti-TIM-1-induced tolerance requires regulatory B cells [J]. Am J Transplant, 2012, 12(8):2072-2078. doi: 10.1111/j.1600-6143.2012.04055.x
    [14] Lee KM, Stott RT, Zhao G, et al. TGF-β-producing regulatory B cells induce regulatory T cells and promote transplantation tolerance [J]. Eur J Immunol, 2014, 44(6):1728-1736. doi: 10.1002/eji.v44.6
    [15] Shah S, Qiao L. Resting B cells expand a CD4+CD25+Foxp3+ Treg population via TGF-beta3 [J]. Eur J Immunol, 2008, 38(9):2488-2498. doi: 10.1002/eji.200838201
    [16] Singh A, Carson WF 4th, Secor ER Jr, et al. Regulatory role of B cells in a murine model of allergic airway disease [J]. J Immunol, 2008, 180(11):7318-7326. doi: 10.4049/jimmunol.180.11.7318
    [17] Li Y, Kim BG, Qian S, et al. Hepatic stellate cells inhibit T cells through active TGF-β1 from a cell surface-bound latent TGF-β1/GARP complex[J]. J Immunol, 2015, 195(6):2648-2656. doi: 10.4049/jimmunol.1500139
  • 加载中
图(2)
计量
  • 文章访问数:  61
  • HTML全文浏览量:  76
  • PDF下载量:  6
  • 被引次数: 0
出版历程
  • 收稿日期:  2016-01-20
  • 网络出版日期:  2021-01-19
  • 刊出日期:  2016-05-15

目录

    /

    返回文章
    返回