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This article is part of the supplement: Proceedings of the 8th Global Arthritis Research Network (GARN) Meeting and 1st Bio-Rheumatology International Congress (BRIC)

Oral presentation

Novel regulatory T cells controlling antibody production and systemic autoimmunity

Kazuhiko Yamamoto*, Tomohisa Okamura and Keishi Fujio

  • * Corresponding author: Kazuhiko Yamamoto

Author Affiliations

Department of Allergy and Rheumatology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan

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Arthritis Research & Therapy 2012, 14(Suppl 1):O31  doi:10.1186/ar3586

The electronic version of this article is the complete one and can be found online at: http://arthritis-research.com/content/14/S1/O31


Published:9 February 2012

© 2012 Yamamoto et al.; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Oral presentation

Regulatory T cells (Tregs) are engaged in the maintenance of immunological self-tolerance and immune homeostasis. IL-10 has an important role in maintaining the normal immune state. We showed that IL-10-secreting Tregs can be delineated in normal mice as CD4+CD25-Foxp3- T cells that express lymphocyte activation gene-3 (LAG-3), an MHC class II-binding CD4 homolog. CD4+CD25-LAG3+ Tregs characteristically express early growth response gene-2 (Egr-2), a key molecule for anergy induction. Retroviral gene transfer of Egr-2 converts naïve CD4+ T cells into IL-10-secreting and LAG-3-expressing Tregs. Moreover, CD4+CD25-LAG3+ Tregs show B cell-dependent development. CD4+CD25-LAG3+ Tregs, but not CD4+CD25+ Tregs, strongly suppressed the antibody production in B cells co-cultured with helper T cells. Thus, IL-10-secreting Egr-2+LAG3+CD4+ Tregs are closely related to B cells and can be exploited for the treat ment of autoimmune diseases.

Systemic lupus erythematosus (SLE) is a multisystem chronic inflammatory disease that affects many organs, and the immunological disorders are accompanied by autoantibody production. Recent case-control association study revealed that polymorphisms in the Egr-2 influence SLE susceptibility in humans. Interestingly, adoptive transfer of CD4+CD25-LAG3+ Tregs from MRL/+ mice suppressed autoantibody production and the progression of nephritis in MRL/lpr lupus prone mice. In contrast, CD4+CD25+ Tregs from MRL/+ mice exhibited no significant therapeutic effect upon transfer to MRL/lpr mice. These results indicate that CD4+CD25-LAG3+ Tregs play key roles in the regulation of humoral immunity by the strong suppressive activity for B cell antibody production.