ICOS共刺激途径中MAPK家族信号分子对活动期SLE患者T细胞增殖及细胞因子分泌的作用  

MAP kinase cascade in ICOS-mediated T cell from active systemic lupus erythematosus patients has distinct functions between cell proliferation and cytokine production

作　　者：蔡刚[1] 杨佳荟[1] 蔡青[2] 汪怀周[1] 赵东宝[2] 韩星海[2] 沈茜[1] 

机构地区：[1]第二军医大学附属长海医院实验诊断科,上海200433 [2]第二军医大学附属长海医院风湿免疫科,上海200433

出　　处：《中华微生物学和免疫学杂志》2007年第9期835-842,共8页Chinese Journal of Microbiology and Immunology

基　　金：国家"863"高技术研究发展计划基金资助(2002AA214091);上海市科委自然科学基金资助(03ZR14026)

摘　　要：目的研究可诱导共刺激分子(ICOS)共刺激途径中丝裂原活化蛋白激酶(MAPK)家族信号分子对活动期系统性红斑狼疮(SLE)患者T细胞增殖及细胞因子分泌的作用。方法体外分离纯化活动期SLE患者和正常人外周总T细胞、CD4^+和CD8^+ T细胞,予以抗CD3/抗ICOS刺激,通过Western blot检测信号分子的活化水平,ELISA检测培养上清细胞因子表达,~3H-TdR法测定细胞的增殖水平。结果活动期SLE病人CD4^+或CD8^+ T细胞经ICOS共刺激后,胞外信号调节激酶(ERK)的活化水平明显低于正常人,CD4^+或总T细胞分泌IL-2明显低于正常人,PD98059抑制ERK活化可致细胞增殖水平下降与IL-2分泌减少,SB-203580抑制p38MAPK活化可致IL-10分泌减少,细胞因子IL-2能明显促进T细胞的增殖水平。结论活动期SLE患者ICOS共刺激T细胞增殖功能降低与其ERK信号活化障碍所致的IL-2分泌减少密切相关,MAPK家族信号分子在ICOS共刺激不同T细胞亚群增殖与细胞因子分泌中具有不同的作用。Objective Although ICOS（ inducible co-stimulator） expression on T-cells from active systemic lupus erythematosus（SLE） patients was higher than that in normal controls, ICOS-mediated proliferation of T cells from the former was lower than the latter. In this study, we attempted to clarify the key signaling molecules of MAP（ mitogen-activated protein） kinase cascades in active SLE patients＇ T cell proliferation and cytokine production, during T cell activation by CD3 induced by co-stimulation with ICOS. Methods Western blot, ELISA, and proliferation assay were used to determine the role of MAP kinase family members such as ERK（ extracellular signal-regulated kinase）, JNK（ c-Jan-N-terminal kinase） and p38 kinase in the process of T cell proliferation and cytokine production. Results ERK regulated T cell proliferation and IL-2 production via ICOS-mediated co-stimulation, while p38 kinase regulated IL-10 production. ERK activation impairment in T cell from active SLE patients contributed to the decrease of IL-2 production and subsequent proliferation. Conclusion MAP kinase family members play distinct roles between T cell cytokine production and cell proliferation via ICOS-mediated co-stimulation. Active SLE patients＇ T-cell produces insufficient IL-2, which is caused by insufficient activation of ERK via ICOS- mediated co-stimulation. This may be one of the factors in T cell resulting in dysfunction in SLE.

关 键 词：系统性红斑狼疮 丝裂原活化蛋白激酶 细胞因子 细胞增殖 可诱导共刺激分子 

分 类 号：R593.241[医药卫生—内科学]