中文摘要：

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。

英文摘要：

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.