Imbalance towards Th1 predominance is associated with acceleration of lupus-like autoimmune syndrome in MRL mice

被引:236
作者
Takahashi, S
Fossati, L
Iwamoto, M
Merino, R
Motta, R
Kobayakawa, T
Izui, S
机构
[1] UNIV GENEVA,CTR MED UNIV,DEPT PATHOL,CH-1211 GENEVA 4,SWITZERLAND
[2] INST TRANSGENOSE,F-45071 ORLEANS,FRANCE
[3] TOKYO WOMENS MED COLL,DEPT INT AFFAIRS & TROP MED,TOKYO 162,JAPAN
关键词
systemic lupus erythematosus; T helper subset; autoantibody; cytokine; mutant mice;
D O I
10.1172/JCI118584
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
To investigate the respective roles of Th1 and Th2 cells in the pathogenesis of lupus-like autoimmune disease, we have analyzed the spontaneous and antigen-induced productions of IgG1 vs IgG2a and IgG3 subclasses in relation to the mRNA expression of INF-gamma (Th1 cytokine promoting IgG2a and IgG3 production), IL-4 (Th2 cytokine promoting IgG1 production), and IL-10 (Th2 cytokine) in CD4(+) T cells from lupus-prone MRL mice, For this purpose, two paired sets of MRL mice were chosen for the comparison of these parameters: (a) MRL-lpr/lpr (lpr for lymphoproliferation) and its recently described substrain with a prolonged survival, termed MRL-lpr/lpr.ll (ll for long lived) and (b) MRL male mice bearing the Yaa (Y-linked autoimmune acceleration) gene (MRL.Yaa) with an accelerated disease and their male counterparts lacking the Yaa gene, We demonstrate herein that the accelerated development of lupus-like autoimmune disease in MRL-lpr/lpr and MRL.Yaa mice, as compared with MRL-lpr/lpr.ll and MRL-+/+ mice, respectively, was correlated with an enhanced expression of IFN-gamma vs IL-4 and IL-10 mRNA in CD4(+) T cells, which paralleled with an increase of spontaneous and foreign T cell-dependent antigen-induced productions of IgG2a and IgG3 vs IgG1 antibodies, These data suggest that an imbalance towards Th1 predominance may play a significant role in the acceleration of lupus-like autoimmune disease in MRL mice.
引用
收藏
页码:1597 / 1604
页数:8
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