近日，美国匹兹堡大学Dario A.A. Vignali及其团队开发出研究CD4⁺常规T细胞的小鼠品系。2021年9月21日，《免疫》杂志在线发表了这项成果。

研究人员表示，CD4⁺T细胞与CD8⁺T细胞有共同的发育途径，在成熟后，CD4⁺T常规T（Tconv）细胞缺乏区别这些细胞与FoxP3⁺T调节细胞的表型标记。

研究人员开发了一个他莫西芬诱导的ThPOK^CreERT2.hCD2品系，在CreERT2-hCD2盒的两侧插入了Frt位点，还有一个Foxp3^Ametrin-FlpO品系，在Foxp3⁺细胞中表达Ametrine和FlpO。繁殖这些小鼠的结果是一个CD4conv^{iCreERT2-hCD2}品系，可以在CD4⁺Tconv细胞中对一个基因进行特异性操作。由于FlpO除去了CreERT2-hCD2盒，CD4⁺Treg细胞不受Cre活性的影响，这被称之为等位基因调节。与能够诱导CD8⁺T细胞的E8I^CreERT2.GFP小鼠比较，以及在黑色素瘤模型中敲除两个抑制性受体PD-1和LAG-3，结果支持这些品系的保真度。

这些工程化小鼠品系为CD4⁺T细胞和CD4⁺Tconv细胞中基因的时间操纵提供了资源。

附：英文原文

Title: A Cre-driven allele-conditioning line to interrogate CD4+ conventional T cells

Author: Lawrence P. Andrews, Kate M. Vignali, Andrea L. Szymczak-Workman, Amanda R. Burton, Erin A. Brunazzi, Shin Foong Ngiow, Akihito Harusato, Arlene H. Sharpe, E. John Wherry, Ichiro Taniuchi, Creg J. Workman, Dario A.A. Vignali

Issue&Volume: 2021-09-21

Abstract: CD4+ T cells share common developmental pathways with CD8+ T cells, and upon maturation, CD4+ T conventional T (Tconv) cells lack phenotypic markers that distinguish these cellsfrom FoxP3+ T regulatory cells. We developed a tamoxifen-inducible ThPOKCreERT2.hCD2 line with Frt sites inserted on either side of the CreERT2-hCD2 cassette, and a Foxp3Ametrine-FlpO strain, expressing Ametrine and FlpO in Foxp3+ cells. Breeding these mice resulted in a CD4conviCreERT2-hCD2 line that allows for the specific manipulation of a gene in CD4+ Tconv cells. As FlpO removes the CreERT2-hCD2 cassette, CD4+ Treg cells are spared from Cre activity, which we refer to as allele conditioning.Comparison with an E8IiCreERT2.GFP mouse that enables inducible targeting of CD8+ T cells, and deletion of two inhibitory receptors, PD-1 and LAG-3, in a melanomamodel, support the fidelity of these lines. These engineered mouse strains presenta resource for the temporal manipulation of genes in CD4+ T cells and CD4+ Tconv cells.

DOI: 10.1016/j.immuni.2021.08.029

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00363-0