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表达小鼠白细胞介素21的Sp2/0细胞体外对鼠肿瘤特异性淋巴细胞增殖及功能的影响

Effect on Murine Tumor Specific Lymphocytes Proliferation and Cytotoxicity by Sp2 /0 Cells Expressing mIL-21 In Vitro
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摘要 目的:研究表达小鼠白细胞介素21(mIL-21)的Sp2/0细胞与用Sp2/0细胞预先免疫的小鼠淋巴细胞体外共培养,是否对预致敏淋巴细胞增殖及功能有影响。方法:获取灭活Sp2/0细胞免疫的小鼠淋巴细胞,在mIL-2存在的条件下,以mIL-21转染的Sp2/0细胞为刺激细胞,用流式细胞术检测CFSE标记的淋巴细胞增殖和7-AAD标记的细胞毒活性;用ELISpot法确定分泌IFN-γ的淋巴细胞数量。结果:转染mIL-21的Sp2/0细胞对预致敏的淋巴细胞增殖有明显影响,活化的淋巴细胞对靶细胞的杀伤率(39.57%±4.72%)与对照组(23.18%±2.94%)相比有较大的提高(P<0.05),且分泌IFN-γ的细胞数量明显增加。活化增殖后的淋巴细胞回输至环磷酰胺预处理的小鼠,能延长小鼠的成瘤时间。结论:表达mIL-21的Sp2/0细胞可有效促进肿瘤抗原特异性淋巴细胞活化及增殖,并增强其对肿瘤细胞的杀伤功能。 Objective: To investigate the influence on murine tumor specific lymphocytes proliferation and cytotoxicity with gene modified Sp2/0 cells expressing mIL-21 in vitro. Methods: Tumor Ag-specific lymphocytes were obtained from pre-immunized BALB/c mice with irradiated Sp2/0 cells, in presence of mIL-2, incubated with the stimulators of inacti-vated mIL-21-modified Sp2/0 cells in vitro. The proliferation and cytotoxic activities of activated lymphocytes were ana- lyzed by flow eytometry respectively staining with CFSE and 7-AAD. The number of IFN-γ-secreting cells was evaluated by ELISpot. Results: The lymphocytes from mice immunized with inactived Sp2/0 cells were obvious proliferative response to Sp2/0 cells expressing mIL-21 in vitro. The killing rate of activated lymphocytes induced by mIL-21-modified Sp2/0 cells on target cells was 35.57%±4.72% and it is increased significantly compared with control group (P〈0.05), and the numbers of Sp2/0 cells secreting IFN-γ was also significant higher than that of the control groups. The activated lympbocytes were transferred to mice pre-treated with cyclophosphamide and the time of mice growing tumor was longer than that of control mice. Conclusion: C, ene modified Sp2/0 cells expressing mIL-21 markedly promote activating and proliferating of lymphocytes from mice immunized with inactived Sp2/0 cells, and enhance cytotoxicity of activated lymphocytes to tumor cells obviously.
出处 《生物技术通讯》 CAS 2009年第1期31-34,共4页 Letters in Biotechnology
基金 江苏省六大人才高峰资助项目(D14)
关键词 小鼠白细胞介素21 肿瘤特异性淋巴细胞 增殖 抗肿瘤作用 mIL-21 tumor specific lymphocyte proliferation anti-tumor activity
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参考文献12

  • 1吴昀,窦骏.T细胞过继免疫治疗恶性实体肿瘤研究进展[J].中国医药生物技术,2008,3(1):62-65. 被引量:5
  • 2Dou Jun, Chu Lili, Zhao Fengshu, et al. Study of immunotherapy of murine myeloma by an IL-21-based tumor vaccine in BALB/c mice[J]. Cancer Biol Ther, 2007,6:12:1871-1879.
  • 3Rutigliano J A, Johnson T R, Hollinger T N, et al. Treatment with anti-LFA-1 delays the CD8^+ cytotoxic-T-lymphocyte response and viral clearance in mice with primary respiratory syncytial virus infection[J]. J Virol, 2004,78(6):3014-3023.
  • 4Lecoeur H, Fevrier M, Garcia S, et al. A novel flow cytometric assay for quantitation and muhiparametric characterization of cell- mediated cytotoxicity[J]. J Immunol Methods, 2001,253(1-2):177-187.
  • 5Strengell M, Matikainen S, Siren J, et al. IL-21 in synergy with IL-15 or IL-18 enhances IFN-3, production in human NK and T cells[J]. J Immunol, 2003,170:5464.
  • 6Zeng R, Spolski R, Finkelstein S E, et al. Synergy of IL-21 and IL-15 in regulating CD8^+ T cell expansion and function[J]. J Exp Med, 2005,201(1):139-148.
  • 7Allard E L, Hardy M P, Leignadier J, et al. Overexpression of IL- 21 promotes massive CD8^+ memory T cell accumulation [J]. Eur J Immunol, 2007,37:3069-3077.
  • 8Ostiguy V, Allard L, Marquis M, et al. IL-21 promotes T lymphocyte survival by activating the phosphatidylinositol-3-kinase signaling cascade[J]. J Leukoc Biol, 2007,82:645-656.
  • 9Moroz A, Eppolito C, Li Q, et al. IL-21 enhances and sustains CD8^+ T cell responses to achieve durable tumor immunity :comparative evaluation of IL-2,IL-15 and IL-21[J]. J Immunol, 2004,173 (2):900-909.
  • 10Alves N L, Arosea F A, van Lier R A. IL-21 sustains CD28 expression on IL-15-activated human naive CD8^+ T cells [J]. J Immunol, 2005,175(2):755-762.

二级参考文献31

  • 1[1]Gottlieb DJ,Micklethwaite K,Bradstock KF,et al.Rapjd expansion of tumor-reactive cells from HLA-matched siblings for adoptive immunotherapy of melanoma.Cytotherapy,2007,9(2):133-143.
  • 2[2]Mackeusen A,Meidenbauer N,Vog1 S,et al.Phase Ⅰ study of adoptive T-cell therapy using antigen-specific CD8+T cells for the treatment of patients with metastatic melanoma.J Clin Oncol,2006,24(31):5060-5069.
  • 3[3]Savage P,Millrain M,Dimakou S,et al.Expansion of CD8+cytotoxic T cells in vitro and in vivo using MHC class Ⅰ tern-diners.Tumour Biol,2007,28(2):70-76.
  • 4[4]Butler MO,Lee JS,Ansén S,et al.Long-lived antitumor CD8+ lymphocytes for adoptive therapy generated using an artificial antigen-presenting cell.Clin Cancer Res,2007,13(6):1857-1867.
  • 5[5]Yamaguchi Y,Ohshita A,Hironaka K,et al.Adoptive immunotherapy using autologous lymphocytes sensitized with HLA class Ⅰ-matched allogeneic tumor cells.Oncol Rep,2006,16(1):165-169.
  • 6[6]Kausche S,Wehler T,Schn(u)rer E,et al.Superior antitumor in vitro responses of allogeneic matched sibling compared with autologous patient CD8+T cells.Cancer Res,2006,66(23):11447-11454.
  • 7[7]Zhao Y,Sun Y,Niu Z,et al.A novel approach to generate host antitumor T cells:adoptive immunotherapy by T cells maturing in xenogeneic thymus.J Immunother(1997),2007,30(1):83-88.
  • 8[8]AJ-Shanti N,Aldahoudi Z.Human purified CD8+T cells:Ex vivo expansion model to generate a maximum yield of functional cytotoxie cells.Immunol Invest,2007,36(1):85-104.
  • 9[9]Ramsborg CG,Papoutsakis ET.Global transcriptional analysis delineates the differential inflammatory response interleukin-15 elicits from cultured human T cells.Exp Hematol,2007,35(3):454-464.
  • 10[10]He H,Wisner P,Yang G,et al.Combined IL-21 and Low-Dose IL-2 therapy induces anti-tumor immunity and long-term curative effects in a murine melanoma tumor model.J Transl Med,2006,4:24.

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