UZH-Logo

Maintenance Infos

Antigens expressed by myelinating glia cells induce peripheral cross-tolerance of endogenous CD8+ T cells


Schildknecht, Anita; Probst, Hans C; McCoy, Kathy D; Miescher, Iris; Brenner, Corinne; Leone, Dino P; Suter, Ueli; Ohashi, Pamela S; van den Broek, Maries (2009). Antigens expressed by myelinating glia cells induce peripheral cross-tolerance of endogenous CD8+ T cells. European Journal of Immunology, 36(6):1505-1515.

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.

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.

Citations

3 citations in Web of Science®
4 citations in Scopus®
Google Scholar™

Altmetrics

Additional indexing

Other titles:
Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:June 2009
Deposited On:27 Jan 2010 10:04
Last Modified:05 Apr 2016 13:17
Publisher:Wiley-Blackwell
ISSN:0014-2980
Additional Information:The definitive version is available at www.blackwell-synergy.com
Publisher DOI:https://doi.org/10.1002/eji.200839019
PubMed ID:19462379

Download

Full text not available from this repository.View at publisher

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations