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

Takahashi, Satoru
Fossati-Jimack, Liliane
Iwamoto, Masahiro
Merino, Ramon
Motta, R.
Kobayakawa, T.
Published in Journal of Clinical Investigation. 1996, vol. 97, no. 7, p. 1597-1604
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 AnimalsAntigens/administration & dosageAutoimmune Diseases/etiology/genetics/ immunologyBase SequenceDNA Primers/geneticsFemaleGene ExpressionHumansImmunoglobulin G/biosynthesis/blood/classificationInterferon-gamma/geneticsInterleukin-10/geneticsInterleukin-4/geneticsLupus Erythematosus, Systemic/etiology/genetics/ immunologyMaleMiceMice, Mutant StrainsMolecular Sequence DataRNA, Messenger/genetics/metabolismTh1 Cells/ immunologyTh2 Cells/immunology
PMID: 8601623
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TAKAHASHI, Satoru et al. Imbalance towards Th1 predominance is associated with acceleration of lupus-like autoimmune syndrome in MRL mice. In: Journal of Clinical Investigation, 1996, vol. 97, n° 7, p. 1597-1604.

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Deposited on : 2010-08-26

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