GATA-3 Expression Is Controlled by TCR Signals and Regulates CD4/CD8 Differentiation
Abstract
GATA-3 is expressed at higher levels in CD4 than in CD8 SP thymocytes. Here we show that upregulation of GATA-3 expression in DP thymocytes is triggered by TCR stimulation, and the extent of upregulation correlates with the strength of the TCR signal. Overexpression of GATA-3 or a partial GATA-3 agonist during positive selection inhibits CD8 SP cell development but is not sufficient to divert class I-restricted T cell precursors to the CD4 lineage. Conversely, expression of the GATA-3 antagonist ROG or of a GATA-3 siRNA hairpin markedly enhances development of CD8 SP cells and reduces CD4 SP development. We propose that GATA-3 contributes to linking the TCR signal strength to the differentiation program of CD4 and CD8 thymocytes.
Additional Information
© 2003 Cell Press. Received 5 November 2002, Revised 28 April 2003, Accepted 30 April 2003, Available online 18 July 2003Published: July 15, 2003. We thank H. Spits (Netherlands Cancer Institute), G. Nolan (Stanford University), and D. Rawlings (UCLA) for the pLZRS vector; L. van Parijs (MIT) for the MIG vector; E. Robey (UC Berkeley) for the MHC-deficient mice; J.Y. Tso (Protein Design labs) for the bispecific F(ab′)_2 antibodies; I.-C. Ho (Harvard) for the ROG cDNA; and J. Rossi (City of Hope) for the RNAi retroviral vector. We also thank S. Pease, B. Kennedy, E. Borucka, S. Qui, and J. Alex of the TAFCIT for timed matings and animal care; R. Diamond and P. Koen of the Cell Sorting Facility for cell sorting; and J. Pomerantz for reading this manuscript. G.H.-H. is a Special Fellow of the Leukemia & Lymphoma Society. J.A.-I is a Cancer Research Institute Investigator. The work was initiated as a Consortium Project of the Stowers Institute for Medical Research and then supported by grants to E.V.R. from the NIH (CA90233) and NSF (MCB-9983129), and to J.A.-I. from the NIH (AI45072) and CRI.Attached Files
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Additional details
- Eprint ID
- 74135
- Resolver ID
- CaltechAUTHORS:20170207-111452870
- Leukemia and Lymphoma Society
- Cancer Research Institute
- Stowers Institute for Medical Research
- CA90233
- NIH
- MCB-9983129
- NSF
- AI45072
- NIH
- Created
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2017-02-07Created from EPrint's datestamp field
- Updated
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2021-11-11Created from EPrint's last_modified field