Chen, Fei and Chen, Dan and Rothenberg, Ellen V. (1999) Specific regulation of Fos family transcription factors in thymocytes at two developmental checkpoints. International Immunology, 11 (5). pp. 677-688. ISSN 0953-8178. http://resolver.caltech.edu/CaltechAUTHORS:20120110-094338292
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A central question in T cell development is what makes cortical thymocytes respond to stimulation in a qualitatively different way than any other thymocyte subset. Part of the answer is that AP-1 function changes drastically at two stages of T cell development. It undergoes striking down-regulation as thymocytes differentiate from immature, CD4^–CD8^– double-negative (DN) TCR^– thymocytes to CD4^+CD8^+ double-positive (DP) TCR^(lo) cortical cells, and then returns in the cells that mature to TCR^(high), CD4^+CD8^– or CD4^–CD8^+ single-positive (SP) thymocytes. At all three stages, the jun family mRNAs can be induced similarly. However, we demonstrate that DP cortical thymocytes are specifically impaired in c-fos and fosB mRNA induction, even when stimuli are used that optimize survival of the cells and a form of in vitro maturation. fra-2 expression is induction independent but much lower in DP cells than in the other subsets. Overall Fos family protein induction accordingly is severely decreased in DP cells. Defective c-Fos and FosB expression in cortical thymocytes is functionally significant, because antibody supershift experiments show that in activated immature and mature thymocytes, most detectable AP-1 DNA-binding complexes do contain c-Fos or FosB. Thus, defective c-Fos and FosB expression in cortical thymocytes qualitatively alters any AP-1 complexes they might express. The cortical thymocytes are not deficient in mRNA expression for any of the constitutive transcription factors that are known to be needed to drive c-Fos or FosB expression, so it is possible that the activity of these factors is developmentally regulated through a post-transcriptional mechanism.
|Additional Information:||© 1999 The Japanese Society for Immunology. Received 7 December 1998, accepted 19 January 1999. We are very grateful to Drs Donna Cohen (Australia National University), Ellen Robey (University of California, Berkeley), Yoichi Shinkai and Fred Alt (Columbia University and Harvard Medical School), and Axel Schonthal (University of Southern California), who generously donated cDNAs and mutant mice for these studies. We also thank Rochelle Diamond, for continuing advice and assistance with cell fractionation, and Inderjit Nangiana, for supporting immunohistochemical studies. Finally, we also thank Dana Miller and Ray Hotz, for excellent care of the mutant mice, and Patrick Koen and Rochelle Diamond, for excellent flow cytometry. These studies were supported by a grant from the USPHS, AI34041. The Caltech Flow Cytometry Facility and the Caltech Biopolymer Synthesis Facility were supported in part by funds from the Beckman Institute at Caltech.|
|Subject Keywords:||AP-1, b-selection, positive selection, T cell development|
|Official Citation:||Fei Chen, Dan Chen, and Ellen V. Rothenberg Specific regulation of Fos family transcription factors in thymocytes at two developmental checkpoints Int. Immunol. (1999) 11(5): 677-688 doi:10.1093/intimm/11.5.677|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Ruth Sustaita|
|Deposited On:||10 Jan 2012 18:39|
|Last Modified:||10 Jan 2012 18:39|
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