PD-L1(hi) retinal pigment epithelium (RPE) cells elicited by inflammatory cytokines induce regulatory activity in uveitogenic T cells.
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| 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 I:C. 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.
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| Authors | Yan Ke, Deming Sun, Guomin Jiang, Henry J Kaplan, Hui Shao |
| Journal | Journal of leukocyte biology (J Leukoc Biol) Vol. 88 Issue 6 Pg. 1241-9 (Dec 2010) ISSN: 1938-3673 [Electronic] England |
| PMID | 20739617 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
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