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Molecular and Cellular Biology, July 2002, p. 4556-4566, Vol. 22, No. 13
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.13.4556-4566.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Increased p300 Expression Inhibits Glucocorticoid Receptor-T-Cell Receptor Antagonism but Does Not Affect Thymocyte Positive Selection

Cheng-Tai Yu,1,2 Ming-Hsien Lin Feng,1 Hsiu-ming Shih,3 and Ming-Zong Lai1,2,4*

Institute of Molecular Biology, Academia Sinica,1 Graduate Institute of Life Science, National Defense Medical School,2 Division of Molecular & Genomic Medicine, National Health Research Institute,3 Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan, Republic of China4

Received 11 February 2002/ Returned for modification 18 March 2002/ Accepted 1 April 2002

Positive selection of T cells is postulated to be dependent on the counterinteraction between glucocorticoid receptor (GR)- and T-cell-receptor (TCR)-induced death signals. In this study we used T-cell-specific expression of p300 to investigate whether GR-TCR cross talk between thymocytes was affected. Activation of the p300-transgenic T cells led to enhanced thymocyte proliferation and increased interleukin 2 production. Thymocyte death, induced by TCR engagement, was no longer prevented by dexamethasone in p300-transgenic mice, indicating an absence of GR-TCR cross-inhibition. This was accompanied by a 50% reduction in the number of thymocytes in p300-transgenic mice. However, the CD4/CD8 profile of thymocytes remained unchanged in p300-transgenic mice. There was no effect on positive selection of the bulk thymocytes or thymocytes with transgenic TCR in p300-transgenic mice. In addition, there was no apparent TCR repertoire "hole" in the selected antigens examined. Our results illustrate a critical role of CBP/p300 in thymic GR-TCR counterinteraction yet do not support the involvement of GR-TCR antagonism in thymocyte positive selection.

* Corresponding author. Mailing address: Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 11529, Taiwan, Republic of China. Phone: (886)-2-2789-9236. Fax: (886)-2-2782-6085. E-mail: mblai{at}ccvax.sinica.edu.tw.

Molecular and Cellular Biology, July 2002, p. 4556-4566, Vol. 22, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.13.4556-4566.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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