The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Genomic expression programs and the integration of the CD28 costimulatory signal in T cell activation
Open accessAbstract
Optimal activation of T cells requires effective occupancy of both the antigen-specific T cell receptor and a second coreceptor such as CD28. We used cDNA microarrays to characterize the genomic expression program in human peripheral T cells responding to stimulation of these receptors. We found that CD28 agonists alone elicited few, but reproducible, changes in gene expression, whereas CD3 agonists elicited a multifaceted temporally choreographed gene expression program. The principal effect of simultaneous engagement of CD28 was to increase the amplitude of the CD3 transcriptional response. The induced genes whose expression was most enhanced by costimulation were significantly enriched for known targets of nuclear factor of activated T cells (NFAT) transcription factors. This enhancement was nearly abolished by blocking the nuclear translocation of NFATc by using the calcineurin inhibitor FK506. CD28 signaling promoted phosphorylation, and thus inactivation, of the NFAT nuclear export kinase glycogen synthase kinase-3 (GSK3), coincident with enhanced dephosphorylation of NFATc proteins. These results provide a detailed picture of the transcriptional program of T cell activation and suggest that enhancement of transcriptional activation by NFAT, through inhibition of its nuclear export, plays a key role in mediating the CD28 costimulatory signal.
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Cites
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Self-citationComplexities of CD28/B7: CTLA-4 Costimulatory Pathways in Autoimmunity and Transplantation
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Cited by
Transcriptional regulation by calcium, calcineurin, and NFAT
Hogan, P. G., Chen, L., Nardone, J., & Rao, A. (2003) · Genes & Development · doi:10.1101/gad.1102703 · Cited by 1,991
Crabtree, G. R., & Olson, E. N. (2002) · Cell · doi:10.1016/s0092-8674(02)00699-2 · Cited by 1,323
Self-citationChemnitz, J. M., Parry, R. V., Nichols, K. E., June, C. H., & Riley, J. L. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.2.945 · Cited by 1,246
Calcium signalling in lymphocyte activation and disease
Feske, S. (2007) · Nature Reviews Immunology · doi:10.1038/nri2152 · Cited by 1,043
CD28 Costimulation: From Mechanism to Therapy
Esensten, J. H., Helou, Y. A., Chopra, G., Weiss, A., & Bluestone, J. A. (2016) · Immunity · doi:10.1016/j.immuni.2016.04.020 · Cited by 937
Metadata
- Authors
- Diehn, M., Alizadeh, A. A., Rando, O. J., Liu, C. L., Stankunas, K., Botstein, D., Crabtree, G. R., & Brown, P. O.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2002-08-23
- Volume
- 99
- Issue
- 18
- Pages
- 11796-11801
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1995181168
- Cited by
- 337
- References
- 46
- FWCI
- 8.96
- Type
- journal article
- Language
- en
- Open access
- green
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- Diehn, M., Alizadeh, A. A., Rando, O. J., Liu, C. L., Stankunas, K., Botstein, D., Crabtree, G. R., & Brown, P. O. (2002). Genomic expression programs and the integration of the CD28 costimulatory signal in T cell activation. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.092284399
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