A genetic method specifically delineates Th1-type Treg cells and their roles in tumor immunity

Regulatory T (Treg) cells expressing the transcription factor (TF) Foxp3 also express other TFs shared by T helper (Th) subsets under certain conditions. Here, to determine the roles of T-bet-expressing Treg cells, we generate a mouse strain, called VeDTR, in which T-bet/Foxp3 double-positive cells are engineered to be spe-cifically labeled and depleted by a combination of Cre-and Flp-recombinase-dependent gene expression control. Characterization of T-bet+Foxp3+ cells using VeDTR mice reveals high resistance under oxidative stress, which is involved in accumulation of T-bet+Foxp3+ cells in tumor tissues. Moreover, short-term deple-tion of T-bet+Foxp3+ cells leads to anti-tumor immunity but not autoimmunity, whereas that of whole Treg cells does both. Although ablation of T-bet+Foxp3+ cells during Toxoplasma infection slightly enhances Th1 immune responses, it does not affect the course of the infection. Collectively, the intersectional genetic method reveals the specific roles of T-bet+Foxp3+ cells in suppressing tumor immunity.

Automated summary

Regulatory T (Treg) cells expressing the transcription factor (TF) Foxp3 also express other TFs shared by T helper (Th) subsets under certain conditions. VeDTR mice are generated to specifically label and deplete T-bet/Foxp3 double-positive cells. T-bet+Foxp3+ cells exhibit high resistance to oxidative stress and accumulate in tumor tissues. Short-term depletion of T-bet+Foxp3+ cells enhances anti-tumor immunity without causing autoimmunity.