<rp id="vgn1y"></rp>
<rp id="vgn1y"><object id="vgn1y"></object></rp>

  • <rp id="vgn1y"><ruby id="vgn1y"><input id="vgn1y"></input></ruby></rp>
  • <th id="vgn1y"></th>
      當前位置:首頁 > 智慧健康列表 > 生物材料研究 > 詳細信息
      小鼠肝臟非實質細胞在誘導Foxp3+CD4+CD25+調節性T細胞及肝移植免疫耐受中起重要作用
      來源: | 作者: | 發布時間:2014-4-15 16:07:58

      小鼠肝臟非實質細胞在誘導Foxp3+CD4+CD25+調節性T細胞及肝移植免疫耐受中起重要作用
      劉宏宇1,關連越1,辛敏剛2,王展鵬1,李卓男1,李巍1,3,Perkins JD3,Reyes  J3
      基金項目:美國華盛頓大學校長基金(李巍);中國國家自然科學基金(李巍81170416;81273264);中國教育部博士點基金(李巍20100061110069);吉林省科技廳國際合作基金(李巍2011742);天普研究基金(李巍01201046);吉林省自然科學基金(李巍201015178) 作者簡介:劉宏宇(1980年生),男,主治醫師,器官移植與免疫耐受 通信聯系人:李巍(1963年生),女,教授,器官移植與免疫耐受.

      (1. 吉林大學中日聯誼醫院肝膽胰外科,長春,130033; 2. 吉林大學中日聯誼醫院麻醉科,長春,130033; 3. 華盛頓大學器官移植外科,西雅圖,美國)

      摘要:我們最近的研究表明Foxp3+CD25+CD4+調節性T (Treg) 細胞在肝移植自發耐受誘導過程中起重要作用,但Treg是如何被誘導的、Treg與其他免疫細胞之間的關系及相互作用仍然不十分清楚。在本研究中, 我們使用供體B6小鼠肝臟非實質細胞(NPC)和樹突狀細胞(DC)在體外與同種異體C3H CD4 T細胞共同培養,以擴增Treg,然后將擴增的Treg輸注給心臟移植受體,通過心臟移植物的存活時間以檢驗Treg的免疫調節功能。通過應用Flt3L-/-小鼠,研究肝臟DC在誘導Treg和肝移植免疫耐受過程中的作用。結果:與脾細胞或脾臟DC相比,肝臟NPC,尤其是DC,在體外與同種異體CD4 T細胞共同培養能夠誘導產生較多的Foxp3+CD25+CD4+Treg。過繼轉輸這些 Treg給同種異體鼠后,能顯著延長與其同品系鼠的心臟移植物存活時間。然而,來自PD-L1-/-鼠的DC卻不能誘導Treg。Flt3L-/- 和 PD-L1-/-小鼠的肝臟移植給C3H會誘導受體抗移植物急性排斥反應。免疫組化染色發現Flt3L-/- 和PD-L1-/-作為供體的肝移植物及受體脾內Foxp3+ Treg細胞明顯減少。結論:肝臟NPC,尤其是肝臟DC在誘導Foxp3+CD25+CD4+Treg和肝移植耐受過程中起重要作用,其機理可能是依賴其表面PD-L1信號傳導通路。
      關鍵詞:肝移植耐受;小鼠;Foxp3+CD4+CD25+ 調節性T細胞;肝臟非實質細胞
      中圖分類號:請查閱《中國圖書館分類法》
      Liver nonparenchymal cells play a significant role in the induction of Foxp3+CD4+CD25+Treg and liver transplantation tolerance in mice
      LIU Hongyu1, GUAN Lianyue1, XIN Mingang2, WANG Zhanpeng1, LI Zhuonan1, LI  Wei1,3, Perkins JD3, Reyes J3
      (1. Dept of Hepatobiliary-pancreatic Surgery,China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun,130033; 2. Anesthesiology,China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun,130033;3. transplant surgery,Washington university, Seattle, USA)
      Abstract: Our recent studies have demonstrated that Foxp3+CD25+CD4+ regulatory T cells (Treg) contribute significantly to liver transplant tolerance induction. It is largely unclear how Treg are induced and how these cells interplay in the regulation of liver transplant tolerance. Here, we attempted to expand the number of Treg in vitro by coculture of liver nonparenchymal cells (NPCs) or dendritic cells (DCs) with allogeneic CD4 T cells, and assessed their function by adoptive transfer to heart allograft recipients. We used Flt3 ligand (FL) mutation mice, which have severe reduction in all types of DCs, to examine the role of liver DCs in liver transplant tolerance in vivo after liver transplantation. Our results showed that liver NPCs, in particular DCs, induced a greater number of Foxp3+ Treg than did spleen cells (SCs) and spleen DCs. Adoptive transfer of the CD25+CD4+ T cells generated from liver NPCs or DCs prolonged heart allograft survival at a significantly higher level than the cells expanded by SCs or spleen DCs. The DCs which isolated from PD-L1-/- mice could not generate Treg in vitro. Moreover, the liver grafts from FL-/- or PD-L1-/- mice were rejected acutely in the C3H recipients and associated with reduction of Foxp3+ cells in the liver grafts and recipient spleens from FL-/- donors. Thus, liver NPCs, in particular DCs, play a critical role in the induction of Treg, which underpin spontaneous acceptance of MHC-mismatched liver allografts in mice.
      Key words: liver transplantation tolerance;mice ;Foxp3+CD4+CD25+Treg;Liver nonparenchymal cells

      奇米色8888