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Publication : A Cre-driven allele-conditioning line to interrogate CD4<sup>+</sup> conventional T cells.

First Author  Andrews LP Year  2021
Journal  Immunity Volume  54
Issue  10 Pages  2209-2217.e6
PubMed ID  34551314 Mgi Jnum  J:312516
Mgi Id  MGI:6790281 Doi  10.1016/j.immuni.2021.08.029
Citation  Andrews LP, et al. (2021) A Cre-driven allele-conditioning line to interrogate CD4(+) conventional T cells. Immunity 54(10):2209-2217.e6
abstractText  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.
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