肝素抑制T细胞活化及机制研究  

Inhibition of heparin to the activation of T lymphocytes and its mechanism

作　　者：张凤[1] 张瑞华[1] 徐薇[1] 储以微[1] 邵先安[1] 熊思东[1] 

机构地区：[1]复旦大学免疫生物学研究所复旦大学医学院免疫学系,上海200032

出　　处：《中国免疫学杂志》2009年第3期197-201,共5页Chinese Journal of Immunology

基　　金：上海市医学领军人才基金(LJ06011);上海市科委基础重点基金(07JC14004);国家自然科学基金(30671952)资助

摘　　要：目的:长期临床实践及动物实验研究发现肝素具有一定抗炎作用,本文旨在阐明其机制是否与抑制T细胞活化过程,以及影响T细胞与抗原递呈细胞间的免疫突触的形成有关。方法:本研究通过氚掺入法检测肝素对T细胞活化增殖的影响,包括丝裂原ConA,超抗原SEA作为刺激剂,此外还有特异性抗原肽;加入外源性IL-2检测肝素抑制T细胞活化与IL-2作用的关系。流式细胞术检测T细胞活化表面标志CD62L的变化;肝素干预下T细胞与抗原递呈细胞间的相互作用,以及T细胞肌动蛋白的聚集情况。结果:在肝素干预下,ConA活化T细胞增殖明显降低并体现出剂量依赖关系,另外SEA、混合淋巴细胞反应以及特异性抗原肽刺激T细胞的增殖也不同程度受到肝素的抑制,外源性IL-2不能挽救被抑制的T细胞。流式细胞检测结果提示肝素干预组T细胞上CD62L表达明显高于对照组。肝素不影响T细胞与抗原递呈细胞之间的作用,也不影响T细胞骨架重排,即免疫突触的形成。结论:肝素抑制T细胞活化及增殖,可能是其抗炎机制的一部分,但并非通过影响T细胞与抗原递呈细胞之间的作用或T细胞活化过程中骨架重排及突触形成。Objective：It is suggested that heparin has the anti-inflammation potential by a series of clinic phenomenon and a number of experiment research.In this study,it is exploited whether heparin inhibits the activation of T lymphocytes to execute anti-inflammation functions,and if so,whether the drug impaires the interaction among T lymphocytes and antigen present cells（APCs）.Methods：3[H] incorporation assay was performed to detect the proliferation of T cells under various stimulators such as ConA,staphylococcal enterotoxin A（SEA）,mixed lymphocyte culture（MLC） and specific antigen peptide in the presence or absence of heparin.The expression of CD62L was determined by utilization of FACS.In addition,immunoflorescences staining was carry out to assess the interaction among T cells and APCs,and the aggregations of actin in T cells was monitored by FACS.In some experiments,exogenous IL-2 was added to detect if IL-2 was involved in the process.Results：Heparin could inhibit propagation of T cells by the incorporation of 3[H] under various stimulators,including ConA,SEA,MLC and specific antigen peptide despite of different concentrations.Meanwhile treatment with heparin inhibited T cells to down-regulate the expression of CD62L on T cells.However,exogenous IL-2 could not restore the proliferation of T cells in the presence of heparin.In addition,the interaction among T cells and APCs was not impaired by the heparin treatment.Moreover,aggregation of actin in T cells was not changed after the treatment of heparin either.Conclusion：Heparin can inhibit the activation and proliferation of T lymphocytes,which may be one of the mechanisms for heparin to exert its effect of anti-inflammation.The inhibitory effect may not be dependent on IL-2,and neither by impacting on the interaction of T cells and APCs,nor by inhibiting the aggregation of actins of T cells.

关 键 词：肝素 T细胞 抗原递呈细胞 肌动蛋白 

分 类 号：R392[医药卫生—免疫学]