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PMID: 9736613 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Evidence implicating Gfi-1 and Pim-1 in pre-T-cell differentiation steps associated with beta-selection.

The EMBO journal ·Vol. 17 ·No. 18 ·1998-09-15 ·Pages 5349-59

Schmidt T, Karsunky H, Rödel B, Zevnik B, Elsässer HP, Möröy T

Abstract

After rearrangement of the T-cell receptor (TCR) beta-locus, early CD4(-)/CD8(-) double negative (DN) thymic T-cells undergo a process termed 'beta-selection' that allows the preferential expansion of cells with a functional TCR beta-chain. This process leads to the formation of a rapidly cycling subset of DN cells that subsequently develop into CD4(+)/CD8(+) double positive (DP) cells. Using transgenic mice that constitutively express the zinc finger protein Gfi-1 and the serine/threonine kinase Pim-1, we found that the levels of both proteins are important for the correct development of DP cells from DN precursors at the stage where 'beta-selection' occurs. Analysis of the CD25(+)/CD44(-,lo) DN subpopulation from these animals revealed that Gfi-1 inhibits and Pim-1 promotes the development of larger beta-selected cycling cells ('L subset') from smaller resting cells ('E subset') within this subpopulation. We conclude from our data that both proteins, Pim-1 and Gfi-1, participate in the regulation of beta-selection-associated pre-T-cell differentiation in opposite directions and that the ratio of both proteins is important for pre-T-cells to pass the 'E' to 'L' transition correctly during beta-selection.

MeSH Terms
Animals CD4 Antigens/analysis CD8 Antigens/analysis Cell Cycle Proteins Cell Differentiation Crosses, Genetic Cyclin-Dependent Kinase Inhibitor p27 DNA-Binding Proteins/analysis,physiology Gene Rearrangement, T-Lymphocyte Genes, bcl-2 Hyaluronan Receptors/analysis Leukopoiesis Mice Mice, Transgenic Microtubule-Associated Proteins/analysis Protein Serine-Threonine Kinases Proto-Oncogene Proteins/analysis,physiology Proto-Oncogene Proteins c-pim-1 Receptors, Antigen, T-Cell, alpha-beta/immunology Receptors, Interleukin-2/analysis T-Lymphocytes/chemistry,immunology Thymus Gland Transcription Factors Tumor Suppressor Proteins
Chemicals
CD4 Antigens CD8 Antigens Cdkn1b protein, mouse Cell Cycle Proteins DNA-Binding Proteins Gfi1 protein, mouse Hyaluronan Receptors Microtubule-Associated Proteins Proto-Oncogene Proteins Receptors, Antigen, T-Cell, alpha-beta Receptors, Interleukin-2 Transcription Factors Tumor Suppressor Proteins Cyclin-Dependent Kinase Inhibitor p27 Pim1 protein, mouse Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-pim-1
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Schmidt T
Institut für Zellbiologie (Tumorforschung), IFZ, Universitätsklinikum Essen, Virchowstrasse 173, D-45122 Essen, Germany.
Karsunky H
Rödel B
Zevnik B
Elsässer H P
Möröy T
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/17.18.5349
Published
1998-09-15
Pages
5349-59
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1170861
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/17.18.5349 PMC Full Text View journal details
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