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Antigen-Specific Blockade of Lethal CD8 T-Cell Mediated Autoimmunity in a Mouse Model of Multiple Sclerosis¹

Shin-Young Na^*, Heike Eujen^*, Kerstin Göbel, Sven G. Meuth, Kati Martens^*, Heinz Wiendl and Thomas Hünig^2,*

^* Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany; and Department of Neurology, University of Würzburg, Würzburg, Germany

Increasing evidence implies CD8 T cells in tissue-specific autoimmune diseases including multiple sclerosis. mAbs specific for MHC class I molecules presenting a dominant autoantigenic peptide may allow selective immunotherapy in such settings. We demonstrate the prophylactic and therapeutic efficacy of such a mAb in a transgenic mouse model of lethal demyelinating disease in which a neo-self Ag expressed by oligodendrocytes is targeted by CD8 T cells with transgenic Ag receptors. Mechanistic studies performed in vitro and in vivo indicate that it is the low expression of MHC class I on oligodendrocytes, which makes this form of Ag-specific intervention possible.

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 Deutsche Forschungsgemeinschaft through SFB581 (to T.H. and H.W.), and Hertie foundation (to T.H.).

² Address correspondence and reprint requests to Dr. Thomas Hünig, Institute for Virology and Immunobiology, University of Würzburg, Verbacher Straße 7, Würzburg, Germany. E-mail address: huenig{at}vim.uni-wuerzburg.de

³ Abbreviations used in this paper: MS, multiple sclerosis; TSA, tissue-specific Ag; MHC I, MHC class I; tg, transgenic; EAE, experimental autoimmune encephalomyelitis; ODC-OVA mice, mice expressing ovalbumin in oligodendrocytes; WT, wild type.

⁴ The online version of this article contains supplementary material.

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