title: Imbalance towards Th1 predominance is associated with acceleration of lupus-like autoimmune syndrome in MRL mice.
abstract: 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.
authors.affiliation: Department of Pathology, Centre Médical Universitaire, University of Geneva, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: L
authors.initials: L
authors.lastname: Fossati
authors.forename: M
authors.initials: M
authors.lastname: Iwamoto
authors.forename: R
authors.initials: R
authors.lastname: Merino
authors.forename: R
authors.initials: R
authors.lastname: Motta
authors.forename: T
authors.initials: T
authors.lastname: Kobayakawa
authors.forename: S
authors.initials: S
authors.lastname: Izui
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D001327:Autoimmune Diseases / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood / Q000145:classification; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000941:Antigens; D017931:DNA Primers; D007074:Immunoglobulin G; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma