葡萄球菌肠毒素A诱导小鼠体内T细胞无能过程中CD28/CTLA-4的变化  

CD28 and CTLA-4 expressions in the process of mice' T-cell inefficiency induced by staphylococcal enterotoxin A

作　　者：黄杨[1] 尹文[2] 张秀敏[1] 司少艳[1] 葛伟[1] 胡沛臻[1] 李侠[1] 隋延仿[1] 

机构地区：[1]第四军医大学西京医院病理科,西安710033 [2]第四军医大学西京医院急诊科,西安710033

出　　处：《解放军医学杂志》2008年第7期844-846,共3页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金资助项目(30271464)

摘　　要：目的在葡萄球菌肠毒素A(SEA)诱导小鼠体内T细胞无能的过程中,观察CD28和CTLA-4的变化规律及相互关系。方法单次(1×SEA组,n=4)或多次(2×SEA组,n=4;3×SEA组,n=4)向小鼠腹腔注射SEA,每次注射间隔3d,分别于末次注射后的第1、3、7、14天,将小鼠处死,制备小鼠脾淋巴细胞。通过流式细胞仪检测细胞膜表达CD28和CTLA-4、细胞内表达CTLA-4和IL-2的阳性率。结果1×SEA组,细胞膜CD28和细胞内IL-2的表达显著上升;而CTLA-4在细胞内和细胞膜表面的表达均降低且无明显变化;2×SEA组CD28和IL-2的表达稍有上升;CTLA-4在细胞内和细胞膜表面的表达均明显增加,胞内CTLA-4的增加尤为显著。3×SEA组,细胞膜CD28、细胞膜和细胞内CTLA-4的表达呈下降趋势,细胞内IL-2在第7天已经检测不到。结论SEA初次诱导小鼠脾淋巴细胞时,能显著促进T细胞的活化;经SEA多次(3次)刺激可诱导T细胞的无反应性。在无能的形成过程中,IL-2产生减少与CD28表达下调可能有着密切联系;CTLA-4的表达上调有利于无能的诱导,但可能不参与无能的维持。Objective To explore the characteristics and regulations of CD28 and CTLA-4 expressions in the process of mice＇ T-cell inefficiency induced by staphylococcal enterotoxin A（SEA）.Methods Twelve mice were averagely divided into three groups（4 each）.The mice in group 1 received single injection of SEA,and the mice in group 2 and 3 received SEA injection twice and three times,respectively,with a 3 days interval.Mice were sacrificed at day 1,3,7 and 14 after the last injection,and then the splenic lymphocytes were isolated.The expressions of CD28 and CTLA-4 in cellular membrane and the intracellular expressions of CTLA-4 and IL-2 were detected with flow cytometry.Results In group 1,the CD28 expression in cellular membrane and the intracellular expression of IL-2 were significantly up-regulated,while the CTLA-4 expressions both in cellular membrane and intracellular expression were lower with no obvious changes.In group 2,the expressions of both CD28 and IL-2 were up-regulated slightly,the expressions of CTLA-4 increased significantly both in cellular membrane and intracellular expression,even more increase was the intracellular CTLA-4 expression.In group 3,the expressions of CD28 and CTAL-4 in cellular membrane and the intracellular CTLA-4 expression declined,and at day 7 the intracellular IL-2 expression was undetectable.Conclusions SEA may obviously promote the activation of naive T-cells when initially used to induce the splenic lymphocytes,while multiple stimulations（e.g.3 times） of SEA may lead T-cells to anergy.On the process of inefficiency,the declined IL-2 production may be closely related to the down-regulation of CD28 expression;the up-regulation of CTLA-4 expression may profit inducing inefficiency,but is not on the maintenance of inefficiency.

关 键 词：超抗原 葡萄球菌肠毒素A(SEA) CD28 CTLA-4 无能 

分 类 号：R392.116[医药卫生—免疫学]