山东大学耳鼻喉眼学报 ›› 2015, Vol. 29 ›› Issue (1): 44-48.doi: 10.6040/j.issn.1673-3770.0.2014.272

• 论著 • 上一篇    下一篇

Foxp3基因转染的Teff细胞抗高危角膜移植排斥的作用

赵军1,2, 刘景1, 王大江3, 陈国玲1, 王琪2, 张晗1   

  1. 1. 山东大学第二医院眼科, 山东 济南 250033;
    2. 辽河油田总医院眼科, 辽宁 盘锦 124010;
    3. 解放军总医院眼科, 北京 100853
  • 收稿日期:2014-08-17 出版日期:2015-02-16 发布日期:2015-02-16
  • 通讯作者: 张晗,教授。E-mail:zhanghan9157@gmail.com E-mail:zhanghan9157@gmail.com
  • 作者简介:赵军。E-mail:zhaojun7837985@sina.com
  • 基金资助:
    山东科技厅博士基金(2008BS03049)

Allograft rejection after high risk corneal transplantation with Foxp3 Gene-transferred effective T cells

ZHAO Jun1 2, LIU Jing1, WANG Da-jiang3, CHEN Guo-ling1, WANG Qi2, ZHANG Han1   

  1. 1. Liaohe Oilfield General Hospital, Panjin 124010, Liaoning, China;
    2. The Second Hospital of Shandong University, Jinan 250033, Shandong, China;
    3. Chinese PLA General Hospital, Beijing 100853, China
  • Received:2014-08-17 Online:2015-02-16 Published:2015-02-16

摘要: 目的 探讨Foxp3基因转染的Teff淋巴细胞在抗高危角膜移植排斥中的作用。方法 将Foxp3基因转染Teff淋巴细胞与Teff淋巴细胞进行混合培养,观察其对Teff淋巴细胞的抑制作用;角膜缝线法诱导Balb/c小鼠产生角膜新生血管,角膜缝线1周后以Balb/c小鼠为受体,以C57/BL6小鼠为供体行穿透性角膜移植,术前1 d尾静脉输入Foxp3基因转染的Teff淋巴细胞。术后,每天观察角膜植片排斥情况;每两周尾静脉取血观察淋巴细胞分型。结果 体外实验显示Foxp3基因转染的Teff淋巴细胞对Teff淋巴细胞具有明显抑制作用;在高危角膜移植小鼠,Foxp3基因转染的Teff淋巴细胞可适当延长植片存活时间(19.71±4.19)d, Treg组角膜植片存活时间(19.28±4.46)d,两组对比差异无统计学意义(P>0.05);空白组角膜存活时间(15.57±2.22),与Foxp3基因转染的Teff细胞组对比,差异有统计学意义(P<0.05);流式细胞学检查显示:FoxP3转染的淋巴细胞可延缓CD4+T淋巴细胞与CD8+T淋巴细胞增殖。结论 转染Foxp3基因的Teff细胞具有抗移植排斥作用。

关键词: 植片排斥, 调节性T细胞, 高危, 穿透性角膜移植, Foxp3基因, 效应性T细胞

Abstract: Objective To observe the effects of Foxp3 gene-transfected Teff lymphocytes against the high-risk corneal transplantation rejection. Methods The Foxp3 gene-transfected Teff lymphocytes and the Teff lymphocytes were cultured together to observe the inhibitory effects on the Teff lymphocytes. Corneal neovascularization was induced by corneal suture in Balb/c mice and after one week, penetrating corneal transplantations were performed while Balb/c mice as receptors and C57/BL6 mice as donors. One day before the surgery, injection of Foxp 3 gene-transfected Teff lymphocytes were performed via tail vein of Balb/c mice. After the surgery, the state of corneal transplantation was monitored on a day to day basis and tail vein blood was sampled once every two weeks to check the lymphocyte types. Results The in vitro experiments showed strong inhibitory effects of Foxp3 gene-transfected Teff lymphocytes on the Teff lymphocytes. To the high-risk corneal transplantation mice, the Foxp3 gene-transfected Teff lymphocytes could moderately extend the survival time of the grafts (19.71±4.19d) while the survival time of the corneal grafts in the Treg group was 19.28±4.46d (P>0.05). On the contrary, the comparison between the Foxp3 gene-transfected Teff lymphocytes and the blank group (15.57± 2.22d) demonstrated some significance (P<0.05). Flow cytology indicated that the Foxp3 gene-transfected lymphocytes could delay the proliferation of CD4+T and CD8+T lymphocytes.Conclusion The Foxp3 gene-transfected Teff lymphocytes could prevent transplant rejection.

Key words: Teff, Treg, High risk, Foxp3 gene, Penetrate cornea transplant, Allograft rejection

中图分类号: 

  • R779.6
[1] Sonoda Y, Streilein, J W.Impaired cell-mediated immunity in mice bearing healthy orthotopic corneal allografts[J]. J Immunol, 1993, 150(5):1727-1734.
[2] Francis J, Till S, Durham S R. Induction of IL-10+CD4+CD25+ T cells by grass pollen immunotherapy[J]. J Allergy Clin Immunol, 2003, 111(6):1255-1261.
[3] Cao D, Malmstrom V, Baecher-Allan C, et al. Isolation and functional characterization of regulatory CD25 bright CD4+ T cells from the target organ of patientswith rheumatoid arthritis[J]. Eur J Immunol, 2003, 33(1):213-215.
[4] Gershon RK, Kondo K. Infectious immunological tolerance[J]. Immunology, 1971, 21(6):903-914.
[5] Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3[J]. Science, 2003, 299(5609):1057-1061.
[6] Fontenot J D, Gavin M A, Rudensky A Y. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells[J]. NatImmunol, 2003, 4(4):330-336.
[7] Khattri R, Cox T, Yasayko S A, et al. An essential role for Scurfin in CD4+CD25+ T regulatory cells[J]. Nat Immunol, 2003, 4(4):337-342.
[8] Karube K, Ohshima K, Tsuchiya T, et al. Expression of FoxP3, a key molecule in CD4CD25 regulatory T cells, in adult T-cell leukaemia/lymphoma cells[J]. Br J Haematol, 2004, 126(1):81-84.
[9] Muthukumar T, Dadhania D, Ding R. Messenger RNA for FoxP3 in the Urine of Renal-Allograft Recipients[J]. N Engl J Med, 2005, 353(22):2342-2351.
[10] Karagiannidis C, Akdis M, Holopainen P, et al. Glucocorticoids upregulate FoxP3 expression and regulatory T cells in asthma[J]. J Allergy Clin Immunol, 2004, 114(6):1425-1433.
[11] Han G, Li Y, Wang J, et al. Active tolerance induction and prevention of autoimmune diabetes by immunogene therapy using recombinant adenoassociated virus expressing glutamic acid decarboxylase 65 peptide GAD(500-585)[J]. J Immunol, 2005, 174(8):4516-4524.
[12] Fontenot J D, Gavin M A, Rudensky A Y. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells[J]. Nat Immunol, 2003, 4(4):330-336.
[13] Walker M R, Kasprowicz D J, Gersuk V H, et al. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells[J]. J Clin Invest, 2003, 112(9):1437-1443.
[14] Apostolou I, von Boehmer H. In vivo instruction of suppressor commitment in naive T cells[J]. J Exp Med, 2004, 199(10):1401-1408.
[15] Curotto de Lafaille M A, Lino A C, Kutchukhidze N, et al. CD25-T cells generate CD25+Foxp3+ regulatory T cells by peripheral expansion[J]. J Immunol, 2004, 173(12):7259-7268.
[16] Cobbold S P, Castejon R, Adams E, et al. Induction of foxP3+ regulatory T cells in the periphery of T cell receptor transgenic mice tolerized to transplants[J]. J Immunol,2004, 172(10):6003-6010.
[17] Mucida D, Kutchukhidze N, Erazo A, et al. Oraltolerance in the absence of naturally occurring Tregs[J]. J Clin Investig, 2005, 115(7):1923-1933.
[18] Kretschmer K, Apostolou I, Hawiger D, et al. Inducing and expanding regulatory T cell populations by foreign antigen[J]. Nat Immunol, 2005, 6(12):1219-1227.
[19] Finney C A, Taylor M D, Wilson M S, et al. Expansion and activation of CD4+CD25+ regulatory T cells in Heligmosomoides polygyrus infection[J]. Eur J Immunol, 2007, 37(7):1874-1886.
[20] Curotto de Lafaille M A, Kutchukhidze N, Shen S, et al. Adap- tive Foxp3+ regulatory T cell-dependent and-independent control of allergic inflammation[J]. Immunity, 2008, 29(1):114-126.
[21] Taams L S, Akbar A N. Peripheral generation and function of CD4+CD25+ regulatory T cells[J]. Curr Top Microbiol Immunol, 2005, 293:115-131.
[22] Curotto de Lafaille M A, Lafaille J J. Natural and adaptive Foxp3+ regulatory T cells: more of the same or a division of labor?[J]. Immunity, 2009, 30(5):626-635.
[23] Viguier M, Lemaître F, Verola O, et al. Foxp3 expressing CD4+CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells[J]. J Immunol, 2004, 173(2):1444-1453.
[1] 王娟,赵敏,徐梅,张琪,周善璧. 外伤致穿透性角膜移植伤口裂开八例并文献复习[J]. 山东大学耳鼻喉眼学报, 2018, 32(2): 95-98.
[2] 朱慧涛, 蔡晓岚, 冯昕, 齐君君, 张金陵, 马越, 李学忠. TSLP与调节性T淋巴细胞在慢性鼻窦炎中的表达[J]. 山东大学耳鼻喉眼学报, 2015, 29(2): 48-51.
[3] 于阅尽, 谭骏, 曹云虹, 张慧, 贾秀华, 叶青. 调节性T细胞与变应性鼻炎特异性脱敏治疗效果的关系[J]. 山东大学耳鼻喉眼学报, 2014, 28(5): 38-41.
[4] 苗北平1,张蕊石2,郭志红3,孙焕吉1,孟庆国1,王晓彬1. 鼻咽癌中VEGF的表达与树突状细胞含量的相关分析及临床意义[J]. 山东大学耳鼻喉眼学报, 2013, 27(4): 62-65.
[5] 庞文会1,时光刚1,时蕾1,王和峰2,王小婷1,韩杰1,李建峰1,王海波1. 调节性T细胞与IgE、IL-4、IL-5在变应性鼻炎小鼠和鼻用激素抗炎中的实验研究[J]. 山东大学耳鼻喉眼学报, 2013, 27(2): 29-33.
[6] 李国俊1,2,潘新良3,雷大鹏3,陈兴明4,陈晓红5,宋西成6. 口咽部鳞状细胞癌与性行为和人乳头状瘤病毒感染[J]. 山东大学耳鼻喉眼学报, 2013, 27(1): 1-7.
[7] 张俊瑶 朱富高 孙美红. 6159例新生儿听力筛查结果分析[J]. 山东大学耳鼻喉眼学报, 2009, 23(4): 38-40.
[8] 鞠秀婷,夏 明 综述, 解 光 审校 . CD4+CD25+调节性T细胞与头颈部肿瘤局部免疫抑制的关系[J]. 山东大学耳鼻喉眼学报, 2007, 21(2): 177-180 .
[9] 夏明,刘?, 张寒冰, 许安廷, 解光 . CD4+C25+Treg细胞与喉鳞状细胞癌的相关性研究[J]. 山东大学耳鼻喉眼学报, 2006, 20(2): 139-142 .
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!