Self-encounters of the third kind: lymph node stroma promotes tolerance to peripheral tissue antigens |
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Institution: | 1. Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts, USA;2. Harvard-MIT Division of Health Sciences and Technology, Boston, Massachusetts, USA;3. Drug Research & Development Center, CGK Co. Ltd, Daejeon, South Korea;4. Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA |
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Abstract: | Multiple mechanisms have evolved to maintain tolerance among CD8+ T cells to innocuous antigens that arise in cutaneous and mucosal tissues. In the thymus, medullary thymic epithelial cells directly present peripheral tissue antigens (PTAs) and incite the deletion of self-reactive thymocytes. Cross-presentation of PTAs by functionally immature, CD8α+ dendritic cells can lead to the deletion of self-reactive CD8+ T cells in secondary lymphoid organs. A third mechanism of deletional tolerance has recently been uncovered in which lymph node-resident stromal cells of non-hematopoietic origin present endogenously expressed PTAs to circulating CD8+ T cells. Emerging data suggest that lymph node stroma is a unique niche for controlling self-reactive T cells. |
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