摘要
目的研究治疗剂量范围内白细胞介素2(IL-2)对T细胞的增殖作用,特别是对人外周血γδT细胞数量和功能亚群的影响。方法采用密度梯度离心法分离人外周血单个核细胞,在不同浓度IL-2作用下培养2周,利用免疫荧光染色和流式细胞术分析培养前后不同淋巴细胞的表型和比例,采用台盼蓝染色和血球计数法进行细胞计数。结果Vδ1和Vδ2型γδT细胞的4个功能亚群中,CD27+细胞(包括CD27+CD45RA+和CD27+CD45RA-)可以表达淋巴组织归巢受体CCR7,CD27-细胞(包括CD27-CD45RA+和CD27-CD45RA-)不表达CCR7,具有分布于外周组织的潜能;各个γδT细胞的功能亚群均能表达活性相关受体,在丝裂原刺激下可以迅速产生不同水平的细胞毒作用相关效应分子。虽然高剂量IL-2对CD4 T细胞的增殖产生抑制作用,但对γδT的增殖反而有促进作用,增殖的γδT细胞以CD27-CD45RA-的效应细胞为主。结论治疗剂量范围内的IL-2具有刺激人外周血γδT细胞增殖的作用,在基于IL-2的抗肿瘤治疗中可能具有重要的生物学意义。
Objective To study the effect of interleukin 2(IL-2)of clinical dose range,on the proliferation of human peripheral blood T cells,with special emphasis on the number and functional phenotype of γδT cells.MethodsHuman peripheral blood mononuclear cells(PBMCs) were isolated by density gradient centrifugation and cultured for 2 weeks at different IL-2 concentrations.Ratio and phenotype of different T cell subpopulations before and after in vitro expansion were explored by immunofluorescence staining.Cell number was estimated by trypan blue staining and cell counting.Results Within the four functional phenotypes of Vδ1 as well as Vδ2 γδT cells,CD27^+ cells(including CD27^+CD45RA+ and CD27^+CD45RA^-subsets) expressed lymphoid tissue homing receptor CCR7,whereas CD27-cells(including CD27-CD45RA+ and CD27^-CD45RA^-subsets) had the peripheral tissue homing potential.All the studied γδT functional subsets showed the expression of activity related receptors,and the ability of a rapid production of various amount of cytotoxicity related effectors following mitogen stimulation.Although IL-2 at high concentration suppressed the proliferation of CD4 T cells,it may promote the proliferation of γδT cells.The proliferated γδT cells were mainly CD27-CD45RA-effector cells.Conclusion IL-2 of the clinical dose range may promote proliferation of human peripheral blood γδT cells,which might have important biological significance in IL-2 based anti-tumor therapy.
出处
《基础医学与临床》
CSCD
北大核心
2010年第5期459-465,共7页
Basic and Clinical Medicine
基金
国家自然科学基金(30972776)