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

Cell Reports (Jul 2023)

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

Journal volume & issue: Vol. 42, no. 7
p. 112813

Abstract

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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.

CP: Immunology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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