Volume 14 Supplement 1

Proceedings of the 8th Global Arthritis Research Network (GARN) Meeting and 1st Bio-Rheumatology International Congress (BRIC)

Open Access

Novel regulatory T cells controlling antibody production and systemic autoimmunity

  • Kazuhiko Yamamoto1,
  • Tomohisa Okamura1 and
  • Keishi Fujio1
Arthritis Research & Therapy201214(Suppl 1):O31

DOI: 10.1186/ar3586

Published: 29 February 2012

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.

Authors’ Affiliations

(1)
Department of Allergy and Rheumatology, The University of Tokyo Graduate School of Medicine

Copyright

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

This article is published under license to 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.

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