特异性细胞因子对T辅助17细胞和T调节性细胞表达的调节作用

摘要

目的 探讨多种细胞因子包括转化生长因子β(TGF-β)、白细胞介素6(IL-6)、白细胞介素2(IL-2)对CD+4T淋巴细胞的分化调节作用.方法 将人外周血T淋巴细胞、鼠脾脏T淋巴细胞在不同的刺激条件下进行体外培养,采用流式细胞仪分析活化T淋巴细胞中CD+4IL-17+T辅助17细胞(Th17细胞)、C+4IL-17+T淋巴细胞、CD+4CD+25FOXP+3T调节性细胞(Treg细胞)的表达情况.结果 鼠脾脏T淋巴细胞培养液中有TGF-β存在时可促进Treg细胞、rh17细胞和CD+8;IL-17+T淋巴细胞分化,表达水平分别为(7.8±2.2)%、(12.6±3.1)%、(10.1±2.6)%.无细胞因子培养的同类细胞为实验对照组,表达水平分别为(4.8±0.6)%、(1.7±0.5)%、(1.0±0.4)%,差异均有统计学意义(q=4.09、8.80、9.61,P<0.05或P<0.01).TGF-β与IL-6细胞因子共同存在时可促进Th17和CD+8IL-17+T淋巴细胞分化,表达水平分别为(17.8±5.3)%、(15.0±4.2)%,而分化受抑制的Treg细胞的表达水平为(4.I±1.2)%,与TGF-β组同类细胞表达水平比较差异均有统计学意义(q=5.03、5.17、5.04,P均<0.01).在TGF-β刺激的T淋巴细胞中加入IL-2细胞因子可使Th17细胞、CD+8;IL-17+T淋巴细胞表达减少,同时伴有Treg细胞表达量的增加;在加入抗IL-2后结果相反,即Th17细胞、CD+8IL-17+T淋巴细胞表达水平增加,Treg细胞表达水平减少.人外周血T淋巴细胞上Th17、CD+8IL-17+、Treg细胞表达水平变化趋势与鼠脾脏淋巴细胞相似.结论 不同细胞因子对于调控Th17细胞和Treg细胞之间的平衡起着十分重要的作用.%Objective To investigate the roles of a variety of cytokines including transforming growth factor beta (TGF-β),interleukin-6 (IL-6) and interleukin-2 (IL-2) in the differentiation of CD+4 Tlymphocyte cells.Methods T lymphocyte cells either in human peripheral blood or routine spleen were cultured in vitro under different stimulation conditions.Flow cytometry was used to analyze the percentages of CD+4IL-17+ T-helper 17(Th17) cells,CD+8 IL-17+ T cells,CD+4 CD+25 FOXP+3 T regulatory (Treg) cells among activated T cells.Results Differentiation of Treg cells,Th17 cells and CD+8 IL-17+ T lymphocyte cells was enhanced when murine splenic T cells were cultured with TGF-β.The levels of expression were (7.8±2.2)%,(12.6±3.1)%,(10.1±2.6)% ,respectively.Experimental control group was severally same type of T cells without cytokine treatment.The levels of expression were (4.8±0.6) %,(1.7±0.5) %,(1.0±0.4) %,respectively.There were statistically significant differences among them (q=4.09,8.80,9.61.P<0.05 or P<0.01).Under combination treatment with IL-6 and TGF-β,(17.8±5.3) % Th17 cells and (15.0±4.2)% CDCD+8 IL-17CD+ T cells were induced,whereas the levels of Treg cells whose differentiation were restrained were (4.1±1.2) %.The differences were statistically significant compared with the level of same type of T cells in TGF-β group (q=5.03,5.17,5.04,P<0.01).Moreover,combination treatment with IL-2 and TGF-β decreased percentages of Th17 and CDCD+8 IL-17CD+ T cells and increased percentages of Treg cells in T cell population.There was an opposite effect when anti-IL-2 was apphed.The percentages of Th17 and CD+8 IL-17+ T cells were increased and the percentages of Treg cells were reduced The regulation trend of T lymphocyte cells in human peripheral blood was similar with those in routine spleen.Conclusion Various cytokines are of great importance in the regulation of the balance between Th17 and Treg cell.