CD28: a signalling perspective
Open accessAbstract
CD28 and the related molecule cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), together with their natural ligands B7.1 and B7.2, have been implicated in the differential regulation of several immune responses. CD28 provides signals during T cell activation which are required for the production of interleukin 2 and other cytokines and chemokines, and it has also been implicated in the regulation of T cell anergy and programmed T cell death. The biochemical signals provided by CD28 are cyclosporin A-resistant and complement those provided by the T cell antigen receptor to allow full activation of T cells. Multiple signalling cascades which may be independent of, or dependent on, protein tyrosine kinase activation have been demonstrated to be activated by CD28, including activation of phospholipase C, p21ras, phosphoinositide 3-kinase, sphingomyelinase/ceramide and 5-lipoxygenase. The relative contributions of these cascades to overall CD28 signalling are still unknown, but probably depend on the state of activation of the T cell and the level of CD28 activation. The importance of these signalling cascades (in particular the phosphoinositide 3-kinase-mediated cascade) to functional indications of CD28 activation, such as interleukin 2 gene regulation, has been investigated using pharmacological and genetic manipulations. These approaches have demonstrated that CD28-activated signalling cascades regulate several transcription factors involved in interleukin 2 transcriptional activation. This review describes in detail the structure and expression of the CD28 and B7 families, the functional outcomes of CD28 ligation and the signalling events that are thought to mediate these functions.
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CD28 signaling is connected to higher Δ133p53 protein, because NF-κB and its downstream mTOR activation may suppress autophagy.
“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 [38]
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- Authors
- WARD, S. G.
- Affiliations
- University of Bath (GB)
- Corresponding author
- WARD, Stephen G
- ORCID
- WARD, Stephen G
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 1996-09-01
- Volume
- 318
- Issue
- 2
- Pages
- 361-377
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1217631
- OpenAlex
- W2404064356
- Cited by
- 149
- References
- 229
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2021: 1 · 2020: 5 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 1 · 2014: 1 · 2013: 2 · 2012: 3
- FWCI
- 1.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- CD28, CTLA-4, CD80, CD86, T cell costimulation, T cell activation, interleukin-2, phosphatidylinositol 3-kinase, phospholipase C, tyrosine kinase, T cell anergy, programmed cell death, signaling pathways, transcription factors, cyclosporine
- MeSH terms
- Abatacept, Amino Acid Sequence, Animals, Antigens, Differentiation, Binding Sites, Chromosome Mapping, Chromosomes, Human, Pair 2, Humans, Lymphocyte Activation, Models, Molecular, Protein-Tyrosine Kinases, T-Lymphocytes, Signal Transduction, Antigens, CD, Consensus Sequence, Apoptosis, Clonal Anergy, Phosphotransferases (Alcohol Group Acceptor), CD28 Antigens, Models, Immunological, Immunoconjugates, Phosphatidylinositol 3-Kinases, CTLA-4 Antigen
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