| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
ß Thymopoiesis1
Department of Immunology, Duke University Medical Center, Durham, NC 27710
TCR gene rearrangement and expression are central to the
development of clonal T lymphocytes. The pre-TCR complex provides the
first signal instructing differentiation and proliferation events
during the transition from
CD4-CD8-TCR- double negative
(DN) stage to CD4+CD8+ double positive (DP)
stage. How the pre-TCR signal leads to downstream gene expression is
not known. HeLa E-box binding protein (HEB), a basic helix-loop-helix
transcription factor, is abundantly detected in thymocytes and is
thought to regulate E-box sites present in many T cell-specific gene
enhancers, including TCR-
, TCR-ß, and CD4. Targeted disruption of
HEB results in a 5- to 10-fold reduction in thymic cellularity that can
be accounted for by a developmental block at the DN to DP stage
transition. Specifically, a dramatic increase in the
CD4low/-CD8+CD5lowHSA+TCRlow/-
immature single positive population and a concomitant decrease in the
subsequent DP population are observed. Adoptive transfer test shows
that this defect is cell-autonomous and restricted to the ß T cell
lineage. Introduction of an ß TCR transgene into the
HEBko/ko background is not sufficient to rescue the
developmental delay. In vivo CD3 cross-linking analysis of thymocytes
indicates that TCR signaling pathway in the HEBko/ko mice
appears intact. These findings suggest an essential function of HEB in
early T cell development, downstream or parallel to the pre-TCR
signaling pathway.
This article has been cited by other articles:
|
|
 |
|
  H.-C. Wang, S. S. Perry, and X.-H. Sun Id1 Attenuates Notch Signaling and Impairs T-Cell Commitment by Elevating Deltex1 Expression Mol. Cell. Biol., September 1, 2009; 29(17): 4640 - 4652. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. del Blanco, J. L. Roberts, N. Zamarreno, N. Balmelle-Devaux, and C. Hernandez-Munain Flexible Stereospecific Interactions and Composition within Nucleoprotein Complexes Assembled on the TCR{alpha} Gene Enhancer J. Immunol., August 1, 2009; 183(3): 1871 - 1883. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yashiro-Ohtani, Y. He, T. Ohtani, M. E. Jones, O. Shestova, L. Xu, T. C. Fang, M. Y. Chiang, A. M. Intlekofer, S. C. Blacklow, et al. Pre-TCR signaling inactivates Notch1 transcription by antagonizing E2A Genes & Dev., July 15, 2009; 23(14): 1665 - 1676. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Ueda-Hayakawa, J. Mahlios, and Y. Zhuang Id3 Restricts the Developmental Potential of {gamma}{delta} Lineage during Thymopoiesis J. Immunol., May 1, 2009; 182(9): 5306 - 5316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. K. Koltsova, M. Ciofani, R. Benezra, T. Miyazaki, N. Clipstone, J. C. Zuniga-Pflucker, and D. L. Wiest Early Growth Response 1 and NF-ATc1 Act in Concert to Promote Thymocyte Development beyond the beta-Selection Checkpoint J. Immunol., October 1, 2007; 179(7): 4694 - 4703. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Fujimoto, T. Ikawa, T. Kina, and Y. Yokota Forced expression of Id2 in fetal thymic T cell progenitors allows some of their progeny to adopt NK cell fate Int. Immunol., October 1, 2007; 19(10): 1175 - 1182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wojciechowski, A. Lai, M. Kondo, and Y. Zhuang E2A and HEB Are Required to Block Thymocyte Proliferation Prior to Pre-TCR Expression J. Immunol., May 1, 2007; 178(9): 5717 - 5726. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Wang, C. L. Claus, G. Vaccarelli, M. Braunstein, T. M. Schmitt, J. C. Zuniga-Pflucker, E. V. Rothenberg, and M. K. Anderson The Basic Helix-Loop-Helix Transcription Factor HEBAlt Is Expressed in Pro-T Cells and Enhances the Generation of T Cell Precursors J. Immunol., July 1, 2006; 177(1): 109 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Puthier, F. Joly, M. Irla, M. Saade, G. Victorero, B. Loriod, and C. Nguyen A General Survey of Thymocyte Differentiation by Transcriptional Analysis of Knockout Mouse Models J. Immunol., November 15, 2004; 173(10): 6109 - 6118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Qi and X.-H. Sun Hyperresponse to T-Cell Receptor Signaling and Apoptosis of Id1 Transgenic Thymocytes Mol. Cell. Biol., September 1, 2004; 24(17): 7313 - 7323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tabrizifard, A. Olaru, J. Plotkin, M. Fallahi-Sichani, F. Livak, and H. T. Petrie Analysis of Transcription Factor Expression during Discrete Stages of Postnatal Thymocyte Differentiation J. Immunol., July 15, 2004; 173(2): 1094 - 1102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ko, J. Ahn, C. Lee, H. Chung, S. H. Jeon, H.-Y. Chung, and R. H. Seong E2A/HEB and Id3 Proteins Control the Sensitivity to Glucocorticoid-induced Apoptosis in Thymocytes by Regulating the SRG3 Expression J. Biol. Chem., May 21, 2004; 279(21): 21916 - 21923. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tremblay, S. Herblot, E. Lecuyer, and T. Hoang Regulation of pTalpha Gene Expression by a Dosage of E2A, HEB, and SCL J. Biol. Chem., April 4, 2003; 278(15): 12680 - 12687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Vaillant, K. Blyth, L. Andrew, J. C. Neil, and E. R. Cameron Enforced Expression of Runx2 Perturbs T Cell Development at a Stage Coincident with {beta}-Selection J. Immunol., September 15, 2002; 169(6): 2866 - 2874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-W. He Orphan nuclear receptors in T lymphocyte development J. Leukoc. Biol., September 1, 2002; 72(3): 440 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Ortman, K. A. Dittmar, P. L. Witte, and P. T. Le Molecular characterization of the mouse involuted thymus: aberrations in expression of transcription regulators in thymocyte and epithelial compartments Int. Immunol., July 1, 2002; 14(7): 813 - 822. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Pan, J. Hanrahan, J. Li, L. P. Hale, and Y. Zhuang An Analysis of T Cell Intrinsic Roles of E2A by Conditional Gene Disruption in the Thymus J. Immunol., April 15, 2002; 168(8): 3923 - 3932. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Reizis and P. Leder The Upstream Enhancer Is Necessary and Sufficient for the Expression of the Pre-T Cell Receptor {alpha} Gene in Immature T Lymphocytes J. Exp. Med., October 1, 2001; 194(7): 979 - 990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Takeuchi, S. Yamasaki, K. Takase, F. Nakatsu, H. Arase, M. Onodera, and T. Saito E2A and HEB Activate the Pre-TCR{alpha} Promoter During Immature T Cell Development J. Immunol., August 15, 2001; 167(4): 2157 - 2163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. T. Le, K. L. Adams, N. Zaya, H. L. Mathews, W. J. Storkus, and T. M. Ellis Human Thymic Epithelial Cells Inhibit IL-15- and IL-2-Driven Differentiation of NK Cells from the Early Human Thymic Progenitors J. Immunol., February 15, 2001; 166(4): 2194 - 2201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Barndt, M. Dai, and Y. Zhuang Functions of E2A-HEB Heterodimers in T-Cell Development Revealed by a Dominant Negative Mutation of HEB Mol. Cell. Biol., September 15, 2000; 20(18): 6677 - 6685. [Abstract] [Full Text]
|
|
|
|
 |
|
 R.J. BARNDT and Y. ZHUANG Controlling Lymphopoiesis with a Combinatorial E-protein Code Cold Spring Harb Symp Quant Biol, January 1, 1999; 64(0): 45 - 50. [Abstract] [PDF]
|
|
|
|
 |
|
 T. Ikawa, S. Fujimoto, H. Kawamoto, Y. Katsura, and Y. Yokota Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2 PNAS, April 24, 2001; 98(9): 5164 - 5169. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
