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Cutting Edge: Regulatory T Cells Directly Suppress B Cells in Systemic Lupus Erythematosus¹

Division of Rheumatology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095

In systemic lupus erythematosus (SLE), adaptive CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Tregs) suppress Th cells that help autoantibody (autoAb)-producing B cells. It is not known whether naturally occurring Tregs can directly suppress B cells in SLE without an intermediate suppression of Th cells. This aspect is important for its implications in the natural course of SLE, because most if not all of the clinical and pathologic effects in SLE are associated with a dysregulated production of autoAbs. In this study, we show that natural Tregs can inhibit B cell activity in vitro and in vivo in SLE through cell contact-mediated mechanisms that directly suppress autoAb-producing B cells, including those B cells that increase numerically during active disease. These results indicate that one way by which natural Tregs attempt to limit humoral autoimmunity in SLE is by directly targeting autoreactive B cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the National Institutes of Health (AR53239 to A.L.C. and AI46776 to B.H.H.), the Southern California Chapter of the Arthritis Foundation (to A.L.C.), and the Arthritis National Research Foundation (to E.V.L.).

² Address correspondence and reprint requests to Prof. Antonio La Cava, Lupus Research Laboratory, Department of Medicine, University of California Los Angeles, 1000 Veteran Avenue 32-59, Los Angeles, California 90095-1670. E-mail address: alacava{at}mednet.ucla.edu

³ Abbreviations used in this paper: SLE, systemic lupus erythematosus; NZB/W, (New Zealand Black x New Zealand White)F₁; Treg, CD4⁺CD25⁺Foxp3⁺ regulatory T cells.