PD-L1(hi) retinal pigment epithelium (RPE) cells elicited by inflammatory cytokines induce regulatory activity in uveitogenic T cells.
J Leukoc Biol
; 88(6): 1241-9, 2010 Dec.
Article
en En
| MEDLINE
| ID: mdl-20739617
ABSTRACT
We previously reported that after exposure to inflammatory cytokines, such as IL-17 and IFN-γ, RPE cells express increased amounts of suppressor of cytokine signaling, leading to general suppression of the inflammatory response. Here, we demonstrate that RPE cells expressed increased levels of PD-L1 in response to IL-17, IFN-γ, or Poly IC. These PD-L1(hi) RPE cells inhibited the pathogenic activities of IRBP-specific T cells, which usually induced uveitis when injected into naïve mice (EAU). The suppressed pathogenicity of these uveitogenic T cells after exposure to PD-L1(hi) RPE cells could be partially reversed by anti-PD-L1 antibodies. Nevertheless, IRBP-specific T cells pre-exposed to PD-L1(hi) RPE cells displayed substantial suppressor activity, which strongly inhibited the activation of fresh IRBP-Teffs in response to subsequent antigenic challenge and when transferred into naïve mice, inhibited the induction of EAU by IRBP-Teff transfer. These findings suggest that inflammatory cytokine-triggered up-regulation of PD-L1 on RPE constitutes a critical factor for inducing infiltrated uveitogenic T cells with regulatory activities, which may accelerate the natural resolution of T cell-mediated intraocular inflammation.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Péptidos
/
Uveítis
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Glicoproteínas de Membrana
/
Linfocitos T
/
Citocinas
/
Antígeno B7-1
/
Epitelio Pigmentado de la Retina
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
J Leukoc Biol
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos