異基因骨髓移植小鼠Treg、NK細胞及相關細胞因子與aGVHD的關系
本文選題:調(diào)節(jié)性T細胞 + NK細胞 ; 參考:《西安交通大學學報(醫(yī)學版)》2017年03期
【摘要】:目的探討異基因骨髓移植小鼠體內(nèi)調(diào)節(jié)性T細胞(Treg)、NK細胞以及與其功能相關的細胞因子白介素-10(IL-10)、轉(zhuǎn)化生長因子(TGF-β)、穿孔素與急性移植物抗宿主病(aGVHD)的關系。方法建立H-2完全不合的C57BL/6→BALB/c純種小鼠間異基因骨髓移植后發(fā)生aGVHD模型。流式細胞儀檢測移植后存活的aGVHD小鼠脾臟CD4+CD25+Treg細胞和NK-1.1+NK細胞的比例;ELISA方法檢測環(huán)孢素A干預aGVHD小鼠血清IL-10、TGF-β和穿孔素的水平,以正常的C57BL/6小鼠為對照。結(jié)果與正常小鼠相比,移植后發(fā)生aGVHD小鼠體內(nèi)Treg細胞比例下降(3.6%vs.1.55%),NK細胞比例上升(3.3%vs.11.5%);環(huán)孢素A治療aGVHD組小鼠,與未干預組相比,血清IL-10水平明顯上升[(125.79±0.27)pg/mL vs.(103.09±3.27)pg/mL,P0.01],TGF-β水平上升但無統(tǒng)計學差異[(252.05±7.84)pg/mL vs.(241.61±15.41)pg/mL,P0.05],穿孔素水平明顯上升[(186.97±4.68)pg/mLvs.(144.35±14.42)pg/mL,P0.01]。結(jié)論 (1)小鼠移植后發(fā)生aGVHD與Treg細胞比例下降有關,Treg功能相關的細胞因子IL-10、TGF-β參與環(huán)孢素A介導的免疫抑制治療;(2)NK細胞參與異基因骨髓移植后aGVHD的發(fā)生過程,穿孔素的水平上升與抑制aGVHD有關。
[Abstract]:Objective to investigate the relationship between regulatory T cell Tregn NK cells and its functional cytokines interleukin-10 (IL-10), transforming growth factor TGF- 尾 (TGF- 尾), perforin and acute graft-versus-host disease (GV HDD) in allogeneic bone marrow transplantation (BMT) mice. Methods A model of aGVHD was established after allogeneic bone marrow transplantation (BMT) in H-2 incompatible C57BL/6 BALB/c mice. The ratio of CD4 CD25 Treg cells to NK-1.1 NK cells in the spleen of surviving aGVHD mice after transplantation was determined by flow cytometry and the levels of IL-10 TGF- 尾 and perforin in serum of aGVHD mice treated with cyclosporine A were detected by Elisa, and the normal C57BL/6 mice were used as control. Results compared with normal mice, the percentage of Treg cells in aGVHD mice after transplantation decreased by 3.6vs.1.55 and the proportion of NK cells increased by 3.3vs.11.50.Cyclosporine A treated aGVHD mice, compared with the non-intervention group, the percentage of NK cells in the mice treated with cyclosporine A was higher than that in the control group. The level of serum IL-10 increased significantly [125.79 鹵3.27pg / mLP0.01], but the level of TGF- 尾 increased without statistical difference [252.05 鹵7.84)pg/mL vs.(241.61 鹵15.41g / mL], and the level of perforin increased obviously [186.97 鹵4.68)pg/mLvs.(144.35 鹵14.42pg / mL-1 P0.01]. Conclusion (1) the relationship between aGVHD and the decrease of Treg cell ratio after transplantation in mice is related to the role of IL-10TGF- 尾 in the development of aGVHD after allogeneic bone marrow transplantation. The cytokine IL-10TGF- 尾 is involved in cyclosporine A-mediated immunosuppressive therapy (Ciclosporin-A-mediated immunotherapy) and NK cells are involved in the development of aGVHD after allogeneic bone marrow transplantation. The increase of perforin level is related to the inhibition of aGVHD.
【作者單位】: 西安交通大學第二附屬醫(yī)院血液科;
【基金】:國家自然科學基金項目資助(No.30800493) 陜西省科技攻關項目(No.2012-K13-02-19)~~
【分類號】:R457.7
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