Schmidt T, Karsunky H, Rödel B, Zevnik B, Elsässer H P, Möröy T
Institut für Zellbiologie (Tumorforschung), IFZ, Universitätsklinikum Essen, Virchowstrasse 173, D-45122 Essen, Germany.
EMBO J. 1998 Sep 15;17(18):5349-59. doi: 10.1093/emboj/17.18.5349.
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.
在T细胞受体（TCR）β基因座重排后，早期CD4(-)/CD8(-)双阴性（DN）胸腺T细胞会经历一个称为“β选择”的过程，该过程允许具有功能性TCRβ链的细胞优先扩增。这个过程导致形成一个快速循环的DN细胞亚群，随后这些细胞发育为CD4(+)/CD8(+)双阳性（DP）细胞。利用组成性表达锌指蛋白Gfi-1和丝氨酸/苏氨酸激酶Pim-1的转基因小鼠，我们发现这两种蛋白的水平对于在“β选择”发生阶段从DN前体正确发育出DP细胞很重要。对这些动物的CD25(+)/CD44(-,lo) DN亚群的分析表明，Gfi-1抑制而Pim-1促进该亚群中较小的静止细胞（“E亚群”）发育为较大的β选择循环细胞（“L亚群”）。我们从数据中得出结论，Pim-1和Gfi-1这两种蛋白都以相反方向参与β选择相关的前T细胞分化调节，并且这两种蛋白的比例对于前T细胞在β选择过程中正确地从“E”过渡到“L”很重要。
