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- W4211151566 abstract "Intrathymic expression of tissue-specific antigens (TSAs) by medullary thymic epithelial cells (Mtecs) leads to deletion of autoreactive T cells. However, because Mtecs are known to be poor antigen-presenting cells (APCs) for tolerance to ubiquitous antigens, and very few Mtecs express a given TSA, it was unclear if central tolerance to TSA was induced directly by Mtec antigen presentation or indirectly by thymic bone marrow (BM)-derived cells via cross-presentation. We show that professional BM-derived APCs acquire TSAs from Mtecs and delete autoreactive CD8 and CD4 T cells. Although direct antigen presentation by Mtecs did not delete the CD4 T cell population tested in this study, Mtec presentation efficiently deleted both monoclonal and polyclonal populations of CD8 T cells. For developing CD8 T cells, deletion by BM-derived APC and by Mtec presentation occurred abruptly at the transitional, CD4high CD8low TCRintermediate stage, presumably as the cells transit from the cortex to the medulla. These studies reveal a cooperative relationship between Mtecs and BM-derived cells in thymic elimination of autoreactive T cells. Although Mtecs synthesize TSAs and delete a subset of autoreactive T cells, BM-derived cells extend the range of clonal deletion by cross-presenting antigen captured from Mtecs. PMID: 15492126 Funding information This work was supported by: NIGMS NIH HHS, United States Grant ID: T32-GM07270 NIGMS NIH HHS, United States Grant ID: T32 GM007270" @default.
- W4211151566 created "2022-02-13" @default.
- W4211151566 creator A5059761327 @default.
- W4211151566 date "2004-11-07" @default.
- W4211151566 modified "2023-09-28" @default.
- W4211151566 title "Faculty Opinions recommendation of Central tolerance to tissue-specific antigens mediated by direct and indirect antigen presentation." @default.
- W4211151566 doi "https://doi.org/10.3410/f.1022119.250700" @default.
- W4211151566 hasPublicationYear "2004" @default.
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