CD4^+CD25^+调节性T细胞在CD46途径下诱导IL-10生成的研究

CD4^+CD25^+ Regulatory T Cells for Inducing Interleukin-10 Production under CD46 Costimulation

目的:炎症抑制因子IL-10在过敏及自身免疫性疾病的发生过程中有着重要意义,补体调节蛋白CD46作为一种新的T细胞活化辅助因子可以诱导CD4+T细胞生成IL-10。另外有研究表明,CD4+CD25+调节性T细胞(CD4+CD25+Tregs)作为一种重要的免疫抑制细胞可以通过促进周围细胞分泌IL-10,使其抑制作用得到放大。本研究探讨在CD46辅助刺激途径下,CD4+CD25+Tregs诱导周围CD4+CD25-T细胞产生IL-10的能力。方法:分离纯化CD4+CD25+Tregs和CD4+CD25-T细胞,采用CD3/CD46或CD3/CD28刺激,分别进行单独培养或按1:10的比例共培养,同时以CD4+T细胞组作为比较。用氚标记胸腺嘧啶核苷(3H-TdR)掺入法测定细胞增殖速率,ELISA方法测定各培养组上清IL-10的水平。结果:在CD46或CD28刺激下,CD4+CD25+Tregs/CD4+CD25-T细胞共培养组、CD4+T细胞组的IL-10水平均显著高于CD4+CD25-T细胞单独培养组。在CD46刺激下,CD4+CD25-T细胞组、CD4+CD25+Tregs/CD4+CD25-T细胞共培养组、CD4+T细胞组IL-10的水平均较CD28刺激下明显增高,各组细胞的增殖能力均较CD28刺激下显著降低。结论:在CD46或CD28刺激下,CD4+CD25+Tregs均能够诱导CD4+CD25-T细胞分泌IL-10,CD46作为一种新的T细胞共刺激分子,与传统的CD28分子相比,能够刺激IL-10分泌增加。本文阐述了CD46途径下CD4+CD25+Tregs诱生IL-10的功能,进一步研究CD46途径下各类免疫细胞的活化反应,对于明确此途径下免疫细胞的功能改变与某些疾病发病机制的关系具有重要意义。

Objective： The suppressive cytokine interleukin-10 （IL-10） plays a central role in allergic and autoimmune diseases. Complement regulatory factor CD46 is a newly found costimulatory molecule for T cell activation, and it can induce IL-10 production in CD4^＋ T cells. The other researches showed CD4^＋CD25^＋regulatory T cells （CD4^＋CD25^＋ Tregs） as an important cells can induce surrounding cells secreting IL-10 so as to enlarge the suppressive function. This study was to investigate IL-10 production by CD4^＋CD25^＋T cells co-cultured with CD4^＋CD25^＋ Tregs under CD46 costimulation. Methods： Purified CD4^＋CD25^＋ Tregs and CD4^＋CD25^＋ T cells were cultured alone or cocultured at a ratio of 1：10 under stimulation with CD3/CD28 or CD3/CD46, undivided CD4~r cells were also cultured under the same condition for comparison. The levels oflL-10, in supematants were assessed by enzyme-linked immunosor- bent assay （ELISA）. Proliferation rates were assayed by （3 H-TdR）thymidine incorporation. Results： Levels of IL-10 in the supematants were higher in cocultured CD4^＋CD25^＋Tregs/CD4^＋CD25T cells and CD4^＋T cells than in CD4^＋CD25 T cells alone, either under CD46 or under CD28 costimulation. Under CD46 costimulation, Levels of IL-10 in CD4^＋CD25^＋ T cells, cocultured cells and CD4^＋T cells were higher than under CD28 costimulation, the proliferation rates were lower than CD28. Conclusion： Under CD46 or CD28 stimulation, CD4^＋CD25^＋ Tregs can induce IL-10 secreting in CD4^＋CD25^＋ T cells, CD46 as a new co-stimulatory signal can activate higher IL-10 se- cretion than traditional signal. This study revealed the function of CD4^＋CD25^＋ Tregs in inducing IL-10 production under CD46 costimulation, thus further researches about activation of immune cells under CD46 pathway are important to identified the relationship of the alterations of immune cells through this new pathway with pathogenesis of some disease.