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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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.
|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|
|Deposited On:||27 Jan 2010 10:04|
|Last Modified:||28 Nov 2013 00:41|
|Additional Information:||The definitive version is available at www.blackwell-synergy.com|
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