天津医药

天津医药 ›› 2016, Vol. 44 ›› Issue (6): 683-686.doi: 10.11958/20150261

• 细胞与分子生物学 • 上一篇    下一篇

干扰素γ增强脂肪间充质干细胞对淋巴细胞的免疫调节作用

王平 1， 顾昕 2， 张娜 3， 张红 1， 师帅南 4， 王玉亮 4   

  1. 1解放军第 254医院骨科 （邮编 300142）； 2解放军空军总医院药学部； 3解放军第 254医院体检中心； 4天津市第一中心医院
  • 收稿日期:2015-10-27 修回日期:2015-12-12 出版日期:2016-06-15 发布日期:2016-07-04
  • 基金资助:
    国家自然科学基金资助项目 （81470982）； 国家临床重点专科建设项目资助课题

Interferon-γ promotes immunomodulatory of adipose tissue-derived mesenchymal stem cells on peripheral blood lymphocytes

WANG Ping1, GU Xin2, ZHANG Na3, ZHANG Hong1, SHI Shuainan4, WANG Yuliang4   

  1. 1 Department of Orthopedics, People’ s Liberation Army No.254 Hospital, Tianjin 300142, China;2 Department of Pharmacy, People’ s Liberation Army Air Force General Hospital;3 Physical Exam Center, People’ s Liberation Army No.254 Hospital; 4 Tianjin First Central Hospital
  • Received:2015-10-27 Revised:2015-12-12 Published:2016-06-15 Online:2016-07-04

PDF (PC)

3801

摘要： 摘要： 目的 观察干扰素 （IFN） -γ增强成人自体脂肪间充质干细胞 （ADSCs） 对外周血淋巴细胞免疫调节的作用及机制。方法 取亲体移植供体术中腹部皮下脂肪组织并留取外周血， 分离单个核细胞 （PBMCs）； 分离、 培养 ADSCs；将 IFN-γ预刺激 ADSCs（IFN-γ预刺激组）及未刺激 ADSCs（未刺激组）分别与 PBMCs 在植物血凝素（PHA） +白细胞介素 （IL） -2 刺激条件下共培养 5 d 后， 用 MTT 法检测活化 T 细胞增殖抑制率， 流式细胞术检测 CD4+CD25+调节性 T细胞（Treg）比例； 实时定量 RT-PCR 法检测 ADSCs 内吲哚胺 2,3 双加氧酶（IDO） mRNA 水平； 观察共培养细胞加入1-甲基色氨酸（1-MT； IDO 阻断组）后活化 T 细胞的增殖能力。结果 分离的自体 ADSCs 高表达 CD73、 CD90、CD105； 具有分化为成脂和成骨细胞的能力。IFN-γ预刺激组 ADSCs 显著增强活化 T 细胞增殖抑制率， 呈剂量依赖关系， 高于未刺激组； IFN-γ预刺激组 CD4+CD25+Treg 比例与未刺激组相比显著升高； IFN-γ预刺激组 ADSCs 内 IDOmRNA 表达水平显著高于未刺激组； IDO 阻断组对活化 T 细胞增殖抑制率较 IFN-γ预刺激组显著降低（P < 0.01）。结论 IFN-γ促进 ADSCs 对活化 T 细胞免疫抑制能力， IDO 在 ADSCs 介导的免疫抑制中起重要免疫调节作用。

关键词: 脂肪组织, 间质干细胞, 间质干细胞移植, 干扰素Ⅱ型, 干扰素γ, 免疫调节, 吲哚胺 2,3 双加氧酶

Abstract: Abstract： Objective To investigate the immunomodulatory effects and the mechanism of interferon (IFN)-γ-pretreated adult autologous adipose tissue-derived mesenchymal stem cells (ADSCs) on peripheral blood lymphocytes. Methods ADSCswere obtained from adult subcutaneous adipose tissues. IFN- γ with and without pretreated ADSCs were used as IFN- γ-pretreated group and IFN-γ-unpretreated group, which were cultured with autologous peripheral blood mononuclear cells (PBMCs) at different concentrations of ADSCs- to- PBMCs ratios in presence of concomitant phytohemagglutinin (PHA)/interleukin (IL)-2 stimulation. After 5 days of culture, the proliferatory inhibitory rate of activated T cells, the percentage of CD4 + CD25 + regulatory T cells (Treg), and the expression of indoleamine 2,3- dioxygenase (IDO) mRNA were assessed.Results ADSCs were isolated from autologous adipose tissue, which strongly expressed CD73, CD90, and CD105, as well as displayed adipogenic and osteogenic differentiation. The percentage of CD4+CD25+Treg was significantly higher in IFN-γ-pretreated group than that of IFN-γ-unpretreated group. The expression level of IDO mRNA in ADSCs was significantlyincreased in IFN-γ-pretreated group than that of IFN-γ-unpretreated group. The proliferation inhibition of activated T cells was significantly decreased in IDO-blocker group than that of IFN- γ-pretreated group (P < 0.01). Conclusion These results suggest that IFN- γ can promote immunosuppressive effects of ADSCs on activated T cells through increased expression of IDO.

Key words: adipose tissue, mesenchymal stem cells, mesenchymal stem cell transplantation, interferon type Ⅱ, interferon-γ, immunomodulatory, indoleamine 2,3-dioxygenase