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Cutting Edge: Multiple Sclerosis-Like Lesions Induced by Effector CD8 T Cells Recognizing a Sequestered Antigen on Oligodendrocytes¹

Amit Saxena^2,*,, Jan Bauer^2,, Tanja Scheikl^*,, Jacques Zappulla^*,, Marc Audebert^*,, Sabine Desbois^*,, Ari Waisman, Hans Lassmann, Roland S. Liblau^3,*, and Lennart T. Mars^*,

^* Institut National de la Santé et de la Recherche Médicale, Unité 563, Toulouse, France; Université Toulouse III, Paul-Sabatier, Toulouse, France; Center for Brain Research, Medical University of Vienna, Vienna, Austria; and First Medical Department, Johannes Gutenberg University, Mainz, Germany

CD8 T cells are emerging as important players in multiple sclerosis (MS) pathogenesis, although their direct contribution to tissue damage is still debated. To assess whether autoreactive CD8 T cells can contribute to the pronounced loss of oligodendrocytes observed in MS plaques, we generated mice in which the model Ag influenza hemagglutinin is selectively expressed in oligodendrocytes. Transfer of preactivated hemagglutinin-specific CD8 T cells led to inflammatory lesions in the optic nerve, spinal cord, and brain. These lesions, associating CD8 T cell infiltration with focal loss of oligodendrocytes, demyelination, and microglia activation, were very reminiscent of active MS lesions. Thus, our study demonstrates the potential of CD8 T cells to induce oligodendrocyte lysis in vivo as a likely consequence of direct Ag-recognition. These results provide new insights with regard to CNS tissue damage mediated by CD8 T cells and for understanding the role of CD8 T cells in MS.

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 European Union Grant LSHM-CT-2005-018637, Institut National de la Santé et de la Recherche Médicale, and the French Multiple Sclerosis Society ARSEP.

² A.S. and J.B. contributed equally to this study.

³ Address correspondence and reprint requests to Dr. Roland Liblau, Institut National de la Santé et de la Recherche Médicale-Unité 563, Hôpital Purpan, Boîte Postale 3028, 31024 Toulouse Cedex 3, France. E-mail address: rolandliblau{at}hotmail.com

⁴ Abbreviations used in this paper: MS, multiple sclerosis; CAII, carbonic anhydrase II; CNPase, cyclic nucleotide 3'-phosphodiesterase; DKI, double knock-in; GrB, granzyme B; HA, hemagglutinin; MOG, myelin oligodendrocyte glycoprotein; MS, multiple sclerosis.

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