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Commentary

The potential of human regulatory T cells generated ex vivo as a treatment for lupus and other chronic inflammatory diseases

David A Horwitz*, J Dixon Gray and Song Guo Zheng

Author Affiliations

The Division of Rheumatology and Immunology, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA

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Arthritis Res 2002, 4:241-246  doi:10.1186/ar414

Published: 12 March 2002

Abstract

Regulatory T cells prevent autoimmunity by suppressing the reactivity of potentially aggressive self-reactive T cells. Contact-dependent CD4+ CD25+ 'professional' suppressor cells and other cytokine-producing CD4+ and CD8+ T-cell subsets mediate this protective function. Evidence will be reviewed that T cells primed with transforming growth factor (TGF)-β expand rapidly following restimulation. Certain CD4+ T cells become contact-dependent suppressor cells and other CD4+ and CD8+ cells become cytokine-producing regulatory cells. This effect is dependent upon a sufficient amount of IL-2 in the microenvironment to overcome the suppressive effects of TGF-β. The adoptive transfer of these suppressor cells generated ex vivo can protect mice from developing chronic graft-versus-host disease with a lupus-like syndrome and alter the course of established disease. These data suggest that autologous T cells primed and expanded with TGF-β have the potential to be used as a therapy for patients with systemic lupus erythematosus and other chronic inflammatory diseases. This novel adoptive immunotherapy also has the potential to prevent the rejection of allogeneic transplants.

Keywords:
autoimmunity; IL-2; regulatory T cells; systemic lupus erythematosus; transforming growth factor-β