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Eur J Immunol. 2009 Jun;39(6):1505-15. doi: 10.1002/eji.200839019.

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

Author information

1
Institute of Experimental Immunology, Zurich, Switzerland. anita_schildknecht@bluewin.ch

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.

PMID:
19462379
DOI:
10.1002/eji.200839019
[Indexed for MEDLINE]
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