IMBALANCE TOWARDS TH1 PREDOMINANCE IS ASSOCIATED WITH ACCELERATION OFLUPUS-LIKE AUTOIMMUNE SYNDROME IN MRL MICE

To investigate the respective roles of Th1 and Th2 cells in the pathog enesis of lupus-like autoimmune disease, we have analyzed the spontane ous and antigen-induced productions of IgG1 vs IgG2a and IgG3 subclass es in relation to the mRNA expression of INF-gamma (Th1 cytokine promo ting IgG2a and IgG3 production), IL-4 (Th2 cytokine promoting IgG1 pro duction), 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 fo r the comparison of these parameters: (a) MRL-lpr/lpr (lpr for lymphop roliferation) and its recently described substrain with a prolonged su rvival, termed MRL-lpr/lpr.ll (ll for long lived) and (b) MRL male mic e bearing the Yaa (Y-linked autoimmune acceleration) gene (MRL.Yaa) wi th 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 w ith 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 predomin ance may play a significant role in the acceleration of lupus-like aut oimmune disease in MRL mice.