6533b7d1fe1ef96bd125c0dd
RESEARCH PRODUCT
Antigens expressed by myelinating glia cells induce peripheral cross‐tolerance of endogenous CD8+T cells
Maries Van Den BroekIris MiescherPamela S. OhashiPamela S. OhashiAnita SchildknechtKathy D. MccoyCorinne BrennerHans Christian ProbstDino P. LeoneUeli Sutersubject
ImmunologyPeripheral toleranceBiologyImmune toleranceCell biologyInterleukin 21medicine.anatomical_structureImmunologymedicineImmunology and AllergyCytotoxic T cellNeurogliaIL-2 receptorAntigen-presenting cellInterleukin 3description
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2009-06-01 | European Journal of Immunology |