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 cells from FoxP3⁺ T regulatory cells. We developed a tamoxifen-inducible ThPOK^CreERT2.hCD2 line with Frt sites inserted on either side of the CreERT2-hCD2 cassette, and a Foxp3^{Ametrine-FlpO} strain, expressing Ametrine and FlpO in Foxp3⁺ cells. Breeding these mice resulted in a CD4conv^{iCreERT2-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 E8I^iCreERT2.GFP mouse that enables inducible targeting of CD8⁺ T cells, and deletion of two inhibitory receptors, PD-1 and LAG-3, in a melanoma model, support the fidelity of these lines. These engineered mouse strains present a resource for the temporal manipulation of genes in CD4⁺ T cells and CD4⁺ Tconv cells.

CD4 ⁺ T细胞共享CD8共同发育途径⁺ T细胞，并且在成熟的CD4 ⁺ Ť常规T（的Tconv）细胞缺乏区别于FoxP3的这些细胞表型标志物⁺调节性T细胞。我们开发了一种他莫昔芬诱导型ThPOK ^CreERT2.hCD2系，其 Frt 位点插入 CreERT2-hCD2 盒的两侧，以及Foxp3 ^{Ametrine-FlpO}菌株，在 Foxp3 ⁺细胞中表达 Ametrine 和 FlpO 。培育这些小鼠产生了 CD4conv ^{iCreERT2-hCD2}系，该系允许对 CD4 ⁺中的基因进行特定操作Tconv 细胞。由于 FlpO 去除了 CreERT2-hCD2 盒，CD4 ⁺ Treg 细胞免受 Cre 活动的影响，我们将其称为等位基因条件反射。与 E8I ^iCreERT2.GFP小鼠进行比较，该小鼠能够诱导 CD8 ⁺ T 细胞靶向，并在黑色素瘤模型中删除两种抑制性受体，PD-1 和 LAG-3，支持这些细胞系的保真度。这些工程小鼠品系为 CD4 ⁺ T 细胞和 CD4 ⁺ Tconv 细胞中基因的时间操作提供了资源。