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Astrocytes protect the CNS: antigen-specific T helper cell responses are inhibited by astrocyte-induced upregulation of CTLA-4 (CD152)

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Abstract

Astrocytes are the first cells that are encountered by T cells invading the central nervous system (CNS) by crossing the blood-brain barrier. We show that primary astrocytes contribute to the immune privilege of the CNS by suppressing Th1 and Th2 cell activation, proliferation and effector function. Moreover, this astrocyte-mediated inhibition of Th effector cells was effective on already activated, proliferating cells. Transforming growth factor (TGF)-β secreted by astrocytes or T cells was not the major factor in the inhibition. The inhibition of T-cell proliferation induced by astrocytes was mainly mediated by upregulation of CTLA-4 on already activated T cells, which occurred both with and without cell-cell contact. Upregulation of the inhibitory molecule CTLA-4 on autoreactive Th cells, as mediated by astrocytes, thus represents a novel mechanism for securing the immune privilege of the CNS.

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Acknowledgements

The authors thank David C. Wraith, University of Bristol, for providing MBP-TCR transgenic mice. We are most grateful to N. Avrion Mitchison, University College London, for critical reading of the manuscript and fruitful discussions. The authors thank Jan Gimsa, University of Rostock, and Asle Sudbø, Norwegian University of Science and Technology, for discussion of the manuscript. Arndt Rolfs, University of Rostock, and Gerd.-R. Burmester, Charité University Hospital (Berlin), are acknowledged for their generous support and helpful discussion. This work was supported by the Gemeinnützige Hertie-Stiftung (1.319.110-01-04 and 191/00/15), the Bundesministerium für Bildung und Forschung (01 ZZ 0108), and the Deutsche Forschungsgemeinschaft SFB 507/B11 and BR 1860/3.

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Authors and Affiliations

  1. Department of Neurology, University of Rostock, Gehlsheimer Strasse 20, 18147 , Rostock, Germany

    Ulrike Gimsa & Daniela Teichmann

  2. Institute of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Olav Kyrres gt. 3, 7489 , Trondheim, Norway

    Anita Øren

  3. Department of Cell and Neurobiology, Institute of Anatomy, Charité University Hospital, 10098 , Berlin, Germany

    Anita Øren, Ingo Bechmann & Robert Nitsch

  4. Deutsches Rheuma-Forschungszentrum Berlin, Schumannstrasse 21–22, 10117 , Berlin, Germany

    Pushpa Pandiyan & Monika C. Brunner-Weinzierl

  5. Department of Rheumatology and Clinical Immunology, Charité University Hospital, 10098 , Berlin, Germany

    Monika C. Brunner-Weinzierl

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  1. Ulrike Gimsa
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Correspondence to Ulrike Gimsa.

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Gimsa, U., Øren, A., Pandiyan, P. et al. Astrocytes protect the CNS: antigen-specific T helper cell responses are inhibited by astrocyte-induced upregulation of CTLA-4 (CD152). J Mol Med 82, 364–372 (2004). https://doi.org/10.1007/s00109-004-0531-6

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  • DOI: https://doi.org/10.1007/s00109-004-0531-6

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