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Schildknecht, A; Probst, H C; McCoy, K D; Miescher, I; Brenner, C; Dino, P; Leone, D; Suter, U; Ohashi, P S; van den Broek, M (2009). Antigens expressed by myelinating glia cells induce peripheral cross-tolerance of endogenous CD8+ T cells. European Journal of Immunology, 36(6):1505-1515.

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Abstract

Auto-reactivity of T cells is largely prevented by central and peripheral tolerance. Nevertheless, immunization with certain self-antigens emulsified in CFA induces autoimmunity in rodents, suggesting that tolerance to some self-antigens is not robust. To investigate the fate of nervous system-specific CD8(+) T cells, which only recently came up as being important contributors for MS pathogenesis, we developed a mouse model that allows inducible expression of lymphocytic choriomeningitis virus-derived CD8(+) T-cell epitopes specifically in oligodendrocytes and Schwann cells, the myelinating glia of the nervous system. These transgenic CD8(+) T-cell epitopes induced robust tolerance of endogenous auto-reactive T cells, which proved thymus-independent and was mediated by cross-presenting bone-marrow-derived cells. Immunohistological staining of secondary lymphoid organs demonstrated the presence of glia-derived antigens in DC, suggesting that peripheral tolerance of CD8(+) T cells results from uptake and presentation by steady state DC.

Other titles:
Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology
DDC:610 Medicine & health
Language:English
Date:June 2009
Deposited On:27 Jan 2010 11:04
Last Modified:28 Nov 2013 01:41
Publisher:Wiley-Blackwell
ISSN:0014-2980
Additional Information:The definitive version is available at www.blackwell-synergy.com
Publisher DOI:10.1002/eji.200839019
PubMed ID:19462379
Citations:Web of Science®. Times Cited: 2
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