Astrocytes protect the CNS: antigen-specific T helper cell responses are inhibited by astrocyte-induced upregulation of CTLA-4 (CD152)
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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.
KeywordsTransgenic mice Lymphocyte activation Neuroimmunomodulation Immune privilege
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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