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Intrinsic and extrinsic control of peripheral T‐cell tolerance by costimulatory molecules of the CD28/ B7 family
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Summary: Positive and negative costimulation by members of the CD28 family is critical for the development of productive immune responses against foreign pathogens and their proper termination to prevent inflammation‐induced tissue damage. In addition, costimulatory signals are critical for the establishment and maintenance of peripheral tolerance. This paradigm has been established in many animal models and has led to the development of immunotherapies targeting costimulation pathways for the treatment of cancer, autoimmune disease, and allograft rejection. During the last decade, the complexity of the biology of costimulatory pathways has greatly increased due to the realization that costimulation does not affect only effector T cells but also influences regulatory T cells and antigen‐presenting cells. Thus, costimulation controls T‐cell tolerance through both intrinsic and extrinsic pathways. In this review, we discuss the influence of costimulation on intrinsic and extrinsic pathways of peripheral tolerance, with emphasis on members of the CD28 family, CD28, cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4), and programmed death‐1 (PD‐1), as well as the downstream cytokine interleukin‐1 (IL‐2).
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“This finding links CD28 function to Δ133p53 upregulation at the protein level, since NF-κB and its activation of mTOR, a major downstream pathway activated by the CD28 signaling, may repress autophagy (36)(37)(38)(39)(40).”
From p53 isoforms regulate aging- and tumor-associated replicative senescence in T lymphocytes (2013) · cites this paper as [37]
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Metadata
- Authors
- Bour‐Jordan, H., Esensten, J. H., Martinez‐Llordella, M., Penaranda, C., Stumpf, M., & Bluestone, J. A.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Bluestone, Jeffrey A.
- Venue
- Immunological Reviews
- Publisher
- Wiley
- Published
- 2011-04-13
- Volume
- 241
- Issue
- 1
- Pages
- 180-205
- ISSN
- 0105-2896 (ISSN-L)
- 1600-065X
- PMC
- PMC3077803
- OpenAlex
- W1907829837
- Cited by
- 391
- References
- 278
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 15 · 2023: 12 · 2022: 13 · 2021: 26 · 2020: 17 · 2019: 23 · 2018: 20 · 2017: 26 · 2016: 34 · 2015: 47 · 2014: 36 · 2013: 49 · 2012: 40
- FWCI
- 4.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Immunological Reviews (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (P01AI035294, R01AI050834, R37AI046643)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK063720)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- peripheral T cell tolerance, CD28/B7 costimulation, CD28, CTLA-4, PD-1, interleukin-2, regulatory T cells, antigen-presenting cells, costimulatory pathways
- MeSH terms
- Animals, Antigen-Presenting Cells, Autoimmune Diseases, Graft Rejection, Humans, Immune Tolerance, Immunotherapy, Neoplasms, Antigens, CD, T-Lymphocyte Subsets, CD28 Antigens, B7-1 Antigen, Receptor Cross-Talk, T-Lymphocytes, Regulatory, Apoptosis Regulatory Proteins, CTLA-4 Antigen, Programmed Cell Death 1 Receptor
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