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

被引:71
作者
Schmidt, T
Karsunky, H
Rödel, B
Zevnik, B
Elsässer, HP
Möröy, T
机构
[1] Univ Essen Gesamthsch Klinikum, IFZ, Inst Zellbiol Tumorforsch, D-45122 Essen, Germany
[2] Univ Marburg, Inst Zytobiol & Zytopathol, D-35033 Marburg, Germany
关键词
D O I
10.1093/emboj/17.18.5349
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:5349 / 5359
页数:11
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