Antigens expressed by myelinating glia cells induce peripheral cross‐tolerance of endogenous CD8+ T cells |
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Authors: | Anita Schildknecht Hans Christian Probst Kathy D McCoy Iris Miescher Corinne Brenner Dino P Leone Ueli Suter Pamela S Ohashi Maries van den Broek |
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Institution: | 1. Institute of Experimental Immunology, Zurich, Switzerland;2. Ontario Cancer Institute, Toronto, Ont., Canada;3. Department of Medical Biophysics, University of Toronto, Toronto, Ont., Canada;4. Department of Immunology, University of Toronto, Toronto, Ont., Canada;5. Institute of Immunology, University of Mainz, Mainz, Germany;6. Institute of Cell Biology, Department of Biology, ETH, Zurich, Switzerland |
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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. |
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Keywords: | Cross‐presentation Cytotoxic T cells Myelinating glia cells |
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