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Cutting Edge: CD25⁺ Regulatory T Cells Prevent Expansion and Induce Apoptosis of B Cells Specific for Tissue Autoantigens¹

Institute of Molecular Medicine and Experimental Immunology, Friedrich-Wilhelms-Universität, Bonn, Germany

To study the role of CD25⁺ regulatory T cells (T_regs) in peripheral B cell tolerance, we generated transgenic rat insulin promoter RIP-OVA/HEL mice expressing the model Ags OVA and HEL in pancreatic islet β cells (where RIP is rat insulin promoter and HEL is hen egg lysozyme). Adoptively transferred transgenic OVA-specific CD4⁺ and CD8⁺ T cells proliferated only in the autoantigen-draining pancreatic lymph node (PLN), demonstrating pancreas-specific Ag expression. Transferred HEL-specific transgenic B cells (IgHEL cells) disappeared within 3 wk from transgenic but not from nontransgenic mice immunized with autoantigen. Depletion of CD25⁺ FoxP3⁺ cells completely restored IgHEL cell numbers. T_reg exerted an analogous suppressive effect on endogenous HEL-specific autoreactive B cells. T_regs acted by inhibiting the proliferation of IgHEL cells in the spleen and PLN and by systemic induction of their apoptosis. Furthermore, they reduced BCR and MHC II surface expression on IgHEL cells in the PLN. These findings demonstrate that autoreactive B cells specific for a nonlymphoid tissue autoantigen are controlled by T_regs.

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 I.L.-P. was supported by fellowship Lu 1387/1-1 of the Deutsche Forschungsgemeinschaft and C.K. by a career development grant of the government of the German state of Nordrhein-Westfalen.

² Address correspondence and reprint requests to Dr. Isis Ludwig-Portugall and Dr. Christian Kurts, Institute of Molecular Medicine and Experimental Immunology, Sigmund Freud Strasse 25, University Clinic, 53105 Bonn, Germany. E-mail addresses: isis_portugall{at}hotmail.com and ckurts{at}web.de

³ Current address: Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037.

⁴ Abbreviations used in this paper: T_reg, regulatory T cell; auto-Ag, autoantigen; HEL, hen egg lysozyme; IgHEL, B cell expressing tg Ig receptor for HEL; LN, lymph node; PLN, pancreatic lymph node; RIP, rat insulin promoter; ROH^high mice, tg mice expressing OVA and HEL under control of RIP; tg, transgenic.

⁵ The online version of this article contains supplemental material.

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