PD-L1-PD-1 Interactions Limit Effector Regulatory T Cell Populations at Homeostasis and During Infection.
Nature immunology(2022)
Abstract
Phenotypic and transcriptional profiling of regulatory T (T-reg) cells at homeostasis reveals that T cell receptor activation promotes T-reg cells with an effector phenotype (eT(reg)) characterized by the production of interleukin-10 and expression of the inhibitory receptor PD-1. At homeostasis, blockade of the PD-1 pathway results in enhanced eT(reg) cell activity, whereas during infection with Toxoplasma gondii, early interferon-gamma upregulates myeloid cell expression of PD-L1 associated with reduced T-reg cell populations. In infected mice, blockade of PD-L1, complete deletion of PD-1 or lineage-specific deletion of PD-1 in T-reg cells prevents loss of eT(reg) cells. These interventions resulted in a reduced ratio of pathogen-specific effector T cells: eT(reg) cells and increased levels of interleukin-10 that mitigated the development of immunopathology, but which could compromise parasite control. Thus, eT(reg) cell expression of PD-1 acts as a sensor to rapidly tune the pool of eT(reg) cells at homeostasis and during inflammatory processes. Perry et al. demonstrate that regulatory T (T-reg) cell function is restrained by the cell-autonomous action of the checkpoint inhibitor molecule PD-1. This PD-1-dependent mechanism tunes T-reg cell function during homeostasis and infection.
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