en
Scientific article
Open access
English

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

Published inThe Journal of clinical investigation, vol. 97, no. 7, p. 1597-1604
Publication date1996
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.

Keywords
  • Animals
  • Antigens/administration & dosage
  • Autoimmune Diseases/etiology/genetics/ immunology
  • Base Sequence
  • DNA Primers/genetics
  • Female
  • Gene Expression
  • Humans
  • Immunoglobulin G/biosynthesis/blood/classification
  • Interferon-gamma/genetics
  • Interleukin-10/genetics
  • Interleukin-4/genetics
  • Lupus Erythematosus, Systemic/etiology/genetics/ immunology
  • Male
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • RNA, Messenger/genetics/metabolism
  • Th1 Cells/ immunology
  • Th2 Cells/immunology
Affiliation Not a UNIGE publication
Citation (ISO format)
TAKAHASHI, Satoru et al. Imbalance towards Th1 predominance is associated with acceleration of lupus-like autoimmune syndrome in MRL mice. In: The Journal of clinical investigation, 1996, vol. 97, n° 7, p. 1597–1604. doi: 10.1172/JCI118584
Main files (1)
Article
accessLevelPublic
Identifiers
ISSN of the journal0021-9738
572views
280downloads

Technical informations

Creation2010/08/26 12:36:48
First validation2010/08/26 12:36:48
Update time2023/03/14 16:01:53
Status update2023/03/14 16:01:52
Last indexation2024/02/12 19:12:26
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack