| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
Departments of
*
Immunology and
Cell Biology and Genetics, Faculty of Medicine, Erasmus University Rotterdam, Rotterdam, The Netherlands; and
Department of Gene Technologies and
Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
The zinc finger transcription factor GATA-3 is of critical
importance for early T cell development and commitment of Th2 cells. To
study the role of GATA-3 in early T cell development, we analyzed and
modified GATA-3 expression in vivo. In mice carrying a targeted
insertion of a lacZ reporter on one allele, we found
that GATA-3 transcription in
CD4+CD8+ double-positive thymocytes
correlated with the onset of positive selection events, i.e., TCR
up-regulation and CD69 expression. LacZ expression
remained high (
80% of cells) during maturation of CD4
single-positive (SP) cells in the thymus, but in developing CD8 SP
cells the fraction of lacZ-expressing cells decreased to
<20%. We modified this pattern by enforced GATA-3
expression driven by the CD2 locus control region, which
provides transcription of GATA-3 throughout T cell
development. In two independent CD2-GATA3-transgenic
lines, 50% of the mice developed thymic lymphoblastoid tumors that
were CD4+CD8+/low
and mostly CD3+. In tumor-free
CD2-GATA3-transgenic mice, the total numbers of CD8 SP
cells in the thymus were within normal ranges, but their maturation was
hampered, as indicated by increased apoptosis of CD8 SP cells and a
selective deficiency of mature
CD69lowHSAlow CD8 SP cells.
In the spleen and lymph nodes, the numbers of
CD8+ T cells were significantly reduced. These
findings indicate that GATA-3 supports development of the CD4 lineage
and inhibits maturation of CD8 SP cells in the
thymus.
This article has been cited by other articles:
|
|
 |
|
  H.-C. Chang, L. Han, R. Jabeen, S. Carotta, S. L. Nutt, and M. H. Kaplan PU.1 Regulates TCR Expression by Modulating GATA-3 Activity J. Immunol., October 15, 2009; 183(8): 4887 - 4894. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wang and R. Bosselut CD4-CD8 Lineage Differentiation: Thpok-ing into the Nucleus J. Immunol., September 1, 2009; 183(5): 2903 - 2910. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Scheinman and O. Avni Transcriptional Regulation of Gata3 in T Helper Cells by the Integrated Activities of Transcription Factors Downstream of the Interleukin-4 Receptor and T Cell Receptor J. Biol. Chem., January 30, 2009; 284(5): 3037 - 3048. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Yin, E. Ladi, S. W. Chan, O. Li, N. Killeen, D. J. Kappes, and E. A. Robey CCR7 Expression in Developing Thymocytes Is Linked to the CD4 versus CD8 Lineage Decision J. Immunol., December 1, 2007; 179(11): 7358 - 7364. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Yamashita, H. Tashimo, H. Ishida, Y. Matsuo, H. Tamauchi, M. Terashima, I. Yoshiwara, S. Habu, and K. Ohta Involvement of GATA-3-dependent Th2 lymphocyte activation in airway hyperresponsiveness Am J Physiol Lung Cell Mol Physiol, June 1, 2006; 290(6): L1045 - L1051. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kohu, T. Sato, S.-i. Ohno, K. Hayashi, R. Uchino, N. Abe, M. Nakazato, N. Yoshida, T. Kikuchi, Y. Iwakura, et al. Overexpression of the Runx3 Transcription Factor Increases the Proportion of Mature Thymocytes of the CD8 Single-Positive Lineage J. Immunol., March 1, 2005; 174(5): 2627 - 2636. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Merkenschlager, S. Amoils, E. Roldan, A. Rahemtulla, E. O'Connor, A. G. Fisher, and K. E. Brown Centromeric Repositioning of Coreceptor Loci Predicts Their Stable Silencing and the CD4/CD8 Lineage Choice J. Exp. Med., December 6, 2004; 200(11): 1437 - 1444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tamauchi, M. Terashima, M. Ito, H. Maruyama, N. Ikewaki, M. Inoue, X. Gao, K. Hozumi, and S. Habu Evidence of GATA-3-dependent Th2 commitment during the in vivo immune response Int. Immunol., January 1, 2004; 16(1): 179 - 187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. S. Hwang, A. Choi, and I-C. Ho Transcriptional Regulation of GATA-3 by an Intronic Regulatory Region and Fetal Liver Zinc Finger Protein 1 J. Immunol., July 1, 2002; 169(1): 248 - 253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Lavenu-Bombled, C. D. Trainor, I. Makeh, P.-H. Romeo, and I. Max-Audit Interleukin-13 Gene Expression Is Regulated by GATA-3 in T Cells. ROLE OF A CRITICAL ASSOCIATION OF A GATA AND TWO GATG MOTIFS J. Biol. Chem., May 17, 2002; 277(21): 18313 - 18321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Kieffer, J. M. Greally, I. Landres, S. Nag, Y. Nakajima, T. Kohwi-Shigematsu, and P. B. Kavathas Identification of a Candidate Regulatory Region in the Human CD8 Gene Complex by Colocalization of DNase I Hypersensitive Sites and Matrix Attachment Regions Which Bind SATB1 and GATA-3 J. Immunol., April 15, 2002; 168(8): 3915 - 3922. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
