Lymph node stroma broaden the peripheral tolerance paradigm
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Research into how self-reactive T cells are tolerized in lymph nodes has focused largely on dendritic cells (DCs). We now know that lymph node stromal cells (LNSC) are important mediators of deletional tolerance to peripheral tissue-restricted antigens (PTAs), which are constitutively expressed and presented by LNSCs. Of the major LNSC subsets, fibroblastic reticular cells and lymphatic endothelial cells are known to directly induce tolerance of responding naïve CD8 T cells. The biological outcome of this interaction fills a void otherwise not covered by DCs or thymic stromal cells. These findings, we suggest, necessitate a broadening of peripheral tolerance theory to include steady-state presentation of clinically relevant PTA to naïve CD8 T cells by lymph node-resident stroma.
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Fibroblasts promote immune tolerance by expression and presentation of normally tissue-restricted antigens.
“In addition, they promote immune tolerance by the expression and presentation of normally tissue-restricted antigens22.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [22]
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- Authors
- Fletcher, A. L., Malhotra, D., & Turley, S. J.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Harvard University (US)
- Corresponding author
- Turley, Shannon J.
- Venue
- Trends in Immunology
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 32
- Issue
- 1
- Pages
- 12-18
- ISSN
- 1471-4906 (ISSN-L)
- PMC
- PMC3163075
- OpenAlex
- W2109445521
- Cited by
- 120
- References
- 69
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 11 · 2019: 6 · 2018: 7 · 2017: 10 · 2016: 10 · 2015: 11 · 2014: 10 · 2013: 7 · 2012: 16
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK074500)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- lymph node stroma, peripheral tolerance, tissue-restricted antigens, fibroblastic reticular cells, lymphatic endothelial cells, CD8+ T cell tolerance, autoreactive T cells, dendritic cells, thymic stromal cells
- MeSH terms
- Animals, Dendritic Cells, Humans, Immune Tolerance, Lymph Nodes, Stromal Cells, Antigen Presentation, CD8-Positive T-Lymphocytes
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