Increased p300 expression inhibits glucocorticoid receptor-T-cell receptor antagonism but does not affect thymocyte positive selection.
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.
Yu
Cheng-Tai
CT
Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan, Republic of China.
Feng
Ming-Hsien Lin
MH
Shih
Hsiu-ming
HM
Lai
Ming-Zong
MZ
D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D004268:DNA-Binding Proteins; D050881:E1A-Associated p300 Protein; D000939:Epitopes; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012097:Repressor Proteins / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins
D015704:CD4 Antigens; D016827:CD8 Antigens; D004268:DNA-Binding Proteins; D000939:Epitopes; D007376:Interleukin-2; D009687:Nuclear Proteins; D011948:Receptors, Antigen, T-Cell; D011965:Receptors, Glucocorticoid; D012097:Repressor Proteins; D015534:Trans-Activators; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse