PD-L1-PD-1 interactions limit effector regulatory T cell populations at homeostasis and during infection.
Nat Immunol
; 23(5): 743-756, 2022 05.
Article
em En
| MEDLINE
| ID: mdl-35437326
ABSTRACT
Phenotypic and transcriptional profiling of regulatory T (Treg) cells at homeostasis reveals that T cell receptor activation promotes Treg cells with an effector phenotype (eTreg) 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 eTreg cell activity, whereas during infection with Toxoplasma gondii, early interferon-γ upregulates myeloid cell expression of PD-L1 associated with reduced Treg cell populations. In infected mice, blockade of PD-L1, complete deletion of PD-1 or lineage-specific deletion of PD-1 in Treg cells prevents loss of eTreg cells. These interventions resulted in a reduced ratio of pathogen-specific effector T cells eTreg cells and increased levels of interleukin-10 that mitigated the development of immunopathology, but which could compromise parasite control. Thus, eTreg cell expression of PD-1 acts as a sensor to rapidly tune the pool of eTreg cells at homeostasis and during inflammatory processes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Toxoplasmose Animal
/
Linfócitos T Reguladores
/
Antígeno B7-H1
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Receptor de Morte Celular Programada 1
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article