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  • Title: Antigens expressed by myelinating glia cells induce peripheral cross-tolerance of endogenous CD8+ T cells.
    Author: Schildknecht A, Probst HC, McCoy KD, Miescher I, Brenner C, Leone DP, Suter U, Ohashi PS, van den Broek M.
    Journal: Eur J Immunol; 2009 Jun; 39(6):1505-15. PubMed ID: 19462379.
    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.
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