LAG-3 Regulatory T Cells Suppress Effector Function of T Cells and Allow Their Proliferation Into Regulatory T Cells.
Journal
Immunology
Series/Report No.
Immunology
ISSN
1365-2567
Date Issued
2025-10-08
Author(s)
Dutta, Avijit
Chen, Tse-Ching
Chang, Chia-Shiang
Huang, Yu-Lin
Lin, Yung-Chang
Lin, Chun-Yen
Huang, Ching-Tai
Abstract
LAG-3 regulatory T cells suppress the effector but not the proliferative response of naïve cognate antigen-specific CD4 T cells in vivo. The Th1, Th2, and Th17 machineries in the suppressed CD4 T cells are impaired. Genomic study of the suppressed T cells revealed enhanced T cell receptor signalling with up-regulation of immune checkpoints, including PD-1 and PD-L1, and down-regulation of pro-inflammatory pathways. Although oxidative metabolism is reduced, the suppressed T cells retain proliferative capacity and acquire LAG-3 expression with proliferation. They acquire the capacity of LAG-3 regulatory T cells. They inhibit the IFN-γ response of co-cultured naïve CD4 T cells in vitro. Upon adoptive transfer, they rescue mice from lethal autoimmune pulmonitis in a dose-dependent manner. Our results implied a mechanism for the maintenance of long-lasting antigen-specific tolerance.
Subjects
LAG‐3+ aTreg cell
effector function‐suppressed proliferation
hemagglutinin‐specific CD4+ T cells
infectious tolerance
SDGs
Publisher
John Wiley and Sons Inc
Type
journal article