CD4 + and CD8 + regulatory T cell characterization in the rat using a unique transgenic Foxp3-EGFP model

Background Regulatory T cells (Treg) in diverse species include CD4 + and CD8 + T cells. In all species, CD8 + Treg have been only partially characterized and there is no rat model in which CD4 + and CD8 + FOXP3 + Treg are genetically tagged. Results We generated a Foxp3-EGFP rat transgenic line in which FOXP3 gene was expressed and controlled EGFP. CD4 + and CD8 + T cells were the only cells that expressed EGFP, in similar proportion as observed with anti-FOXP3 antibodies and co-labeled in the same cells. CD4 + EGFP + Treg were 5–10 times more frequent than CD8 + EGFP + Treg. The suppressive activity of CD4 + and CD8 + Treg was largely confined to EGFP + cells. RNAseq analyses showed similarities but also differences among CD4 + and CD8 + EGFP + cells and provided the first description of the natural FOXP3 + CD8 + Treg transcriptome. In vitro culture of CD4 + and CD8 + EGFP − cells with TGFbeta and IL-2 generated induced EGFP + Treg. CD4 + and CD8 + EGFP + Treg were expanded upon in vivo administration of a low dose of IL-2. Conclusions This new and unique rat line constitutes a useful model to identify and isolate viable CD4 + and CD8 + FOXP3 + Treg. Additionally, it allows to identify molecules expressed in CD8 + Treg that may allow to better define their phenotype and function not only in rats but also in other species.