A genetic method specifically delineates Th1-type Treg cells and their roles in tumor immunity
Masaaki Okamoto,
Miwa Sasai,
Ayumi Kuratani,
Daisuke Okuzaki,
Masaya Arai,
James B. Wing,
Shimon Sakaguchi,
Masahiro Yamamoto
Affiliations
Masaaki Okamoto
Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan
Miwa Sasai
Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; Department of Immunoparasitology, Center for Infectious Disease Education and Research, Osaka University, Suita, Osaka 565-0871, Japan
Ayumi Kuratani
Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan
Daisuke Okuzaki
Genome Information Research Center, Osaka University, Suita, Osaka 565-0871, Japan
Masaya Arai
Laboratory of Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan
James B. Wing
Laboratory of Human Immunology (Single Cell Immunology), WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; Human Immunology Team, Center for Infectious Disease Education and Research, Osaka University, Suita, Osaka 565-0871, Japan
Shimon Sakaguchi
Laboratory of Experimental Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan
Masahiro Yamamoto
Department of Immunoparasitology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan; Laboratory of Immunoparasitology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan; Department of Immunoparasitology, Center for Infectious Disease Education and Research, Osaka University, Suita, Osaka 565-0871, Japan; Corresponding author
Summary: 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 specifically 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 depletion 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.
