Regulation of T-cell lymphokine gene transcription by the accessory molecule CD28 - PubMed (original) (raw)

Regulation of T-cell lymphokine gene transcription by the accessory molecule CD28

J D Fraser et al. Mol Cell Biol. 1992 Oct.

Abstract

T-cell activation results in the production of multiple lymphokines. Efficient lymphokine gene expression appears to require both T-cell antigen receptor (TCR) signal transduction and an uncharacterized second or costimulatory signal. CD28 is a T-cell differentiation antigen that can generate intracellular signals that synergize with those of the TCR to increase T-cell activation and interleukin-2 (IL-2) gene expression. In these studies, we have examined the effect of CD28 signal transduction on granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3), and gamma interferon (IFN-gamma) promoter activity. Stimulation of CD28 in the presence of TCR-like signals increases the activity of the GM-CSF, IL-3, and IFN-gamma promoters by three- to sixfold. As previously demonstrated for the IL-2 promoter, the IL-3 and GM-CSF promoters contain distinct elements of similar sequence which specifically bind a CD28-induced nuclear complex. Mutation of the CD28 response elements in the IL-3 and GM-CSF promoters abrogates the CD28-induced activity without affecting phorbol ester- and calcium ionophore-induced activity. UV cross-linking indicates that the CD28-induced nuclear complex contains polypeptides of approximately 35, 36, and 44 kDa. These studies indicate that the TCR and CD28-regulated signal transduction pathways coordinately regulate the transcription of several lymphokines and that the influence of CD28 signals on transcription is mediated by a common complex.

PubMed Disclaimer

Cited by

Divergent effects of T cell costimulation and inflammatory cytokine production on autoimmune peripheral neuropathy provoked by Aire deficiency.
Zeng XL, Nagavalli A, Smith CJ, Howard JF, Su MA. Zeng XL, et al. J Immunol. 2013 Apr 15;190(8):3895-904. doi: 10.4049/jimmunol.1203001. Epub 2013 Mar 13. J Immunol. 2013. PMID: 23487421 Free PMC article.
CD28/CTLA-4 and CD80/CD86 families: signaling and function.
Slavik JM, Hutchcroft JE, Bierer BE. Slavik JM, et al. Immunol Res. 1999;19(1):1-24. doi: 10.1007/BF02786473. Immunol Res. 1999. PMID: 10374692 Review.
Defective integration of activating signals derived from the T cell receptor (TCR) and costimulatory molecules in both CD4+ and CD8+ T lymphocytes of common variable immunodeficiency (CVID) patients.
Thon V, Wolf HM, Sasgary M, Litzman J, Samstag A, Hauber I, Lokaj J, Eibl MM. Thon V, et al. Clin Exp Immunol. 1997 Nov;110(2):174-81. doi: 10.1111/j.1365-2249.1997.tb08314.x. Clin Exp Immunol. 1997. PMID: 9367399 Free PMC article.
Transcription of the interleukin 4 gene is regulated by multiple promoter elements.
Todd MD, Grusby MJ, Lederer JA, Lacy E, Lichtman AH, Glimcher LH. Todd MD, et al. J Exp Med. 1993 Jun 1;177(6):1663-74. doi: 10.1084/jem.177.6.1663. J Exp Med. 1993. PMID: 8496684 Free PMC article.
Calcineurin potentiates activation of the granulocyte-macrophage colony-stimulating factor gene in T cells: involvement of the conserved lymphokine element 0.
Tsuboi A, Masuda ES, Naito Y, Tokumitsu H, Arai K, Arai N. Tsuboi A, et al. Mol Biol Cell. 1994 Jan;5(1):119-28. doi: 10.1091/mbc.5.1.119. Mol Biol Cell. 1994. PMID: 8186461 Free PMC article.

References

1. J Immunol. 1991 Apr 1;146(7):2426-33 - PubMed
1. J Exp Med. 1992 Feb 1;175(2):353-60 - PubMed
1. J Exp Med. 1991 Mar 1;173(3):759-62 - PubMed
1. Nature. 1990 Aug 2;346(6283):425-34 - PubMed
1. Proc Natl Acad Sci U S A. 1990 Jul;87(13):5031-5 - PubMed

Regulation of T-cell lymphokine gene transcription by the accessory molecule CD28 - PubMed (original) (raw)