May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
The Role of Programmed Death-1 (PD-1)/PD-L Pathway in Regulation of Murine Experimental Autoimmune Uveoretinitis (EAU)
Author Affiliations & Notes
  • Y. Usui
    Ophthalmology, Tokyo Medical Univ Hospital, Shinjuku-ku, Japan
  • M. Takeuchi
    Ophthalmology, Tokyo Medical Univ Hospital, Shinjuku-ku, Japan
  • Y. Okunuki
    Ophthalmology, Tokyo Medical Univ Hospital, Shinjuku-ku, Japan
  • T. Kezuka
    Ophthalmology, Tokyo Medical Univ Hospital, Shinjuku-ku, Japan
  • T. Hattori
    Ophthalmology, Tokyo Medical Univ Hospital, Shinjuku-ku, Japan
  • J. Ma
    Ophthalmology, Tokyo Medical Univ Hospital, Shinjuku-ku, Japan
  • C. Nishiyama
    Atopy Research Center,
    Juntendo University, bunkyo-ku, Japan
  • T. Okazaki
    Immunology and Genomic Medicine, Kyoto University, Sakyo-ku, Japan
  • T. Honjo
    Immunology and Genomic Medicine, Kyoto University, Sakyo-ku, Japan
  • H. Akiba
    Immunology,
    Juntendo University, bunkyo-ku, Japan
  • H. Goto
    Ophthalmology, Tokyo Medical Univ Hospital, Shinjuku-ku, Japan
  • Footnotes
    Commercial Relationships  Y. Usui, None; M. Takeuchi, None; Y. Okunuki, None; T. Kezuka, None; T. Hattori, None; J. Ma, None; C. Nishiyama, None; T. Okazaki, None; T. Honjo, None; H. Akiba, None; H. Goto, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3882. doi:https://doi.org/
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      Y. Usui, M. Takeuchi, Y. Okunuki, T. Kezuka, T. Hattori, J. Ma, C. Nishiyama, T. Okazaki, T. Honjo, H. Akiba, H. Goto; The Role of Programmed Death-1 (PD-1)/PD-L Pathway in Regulation of Murine Experimental Autoimmune Uveoretinitis (EAU). Invest. Ophthalmol. Vis. Sci. 2008;49(13):3882. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Experimental autoimmune uveitis (EAU) has been used as a model for human uveitis in relation to the autoimmune mechanism and proved to be a T-cell mediated autoimmune disease. The CD28 homologue programmed death-1 (PD-1) and its ligands, PD-L1 and PD-L2 (which are homologous to B7), constitute an inhibitory pathway of T cell costimulation. The PD-1 pathway is of interest for immune-mediated diseases given that PD-1 deficient mice develop autoimmune diseases. Here, we aimed to examine whether PD-1 pathway is involved in regulation for development of murine EAU.

Methods: : To develop EAU, wild type or PD-1 deficient C57BL/6 mice were immunized with IRBP peptide 1-20 (IRBP-p) in CFA with M. tuberculosis H37RA and were injected i.p. with pertussis toxin. In some experiments, wild-type mice received antagonistic anti-PD-1 mAb three times on every other day prior to immunization were also used. Severity of EAU was evaluated clinically and histopathologically on day 21 after immunization. T cells were also collected from immunized mice on day 21, and measured for proliferation responses and cytokine production by stimulation with IRPB-p.

Results: : Severity of EAU was significantly exacerbated both clinically and histopathologically in PD-1 deficient mice compared with wild-type mice. T cell proliferation responses to IRBP-p were remarkably higher in PD-1 deficient mice than that of wild-type mice. As well as T cell proliferation responses, IL-17 and IFN-γ production by T cells stimulated with IRBP-p were strikingly more in PD-1 deficient mice than that of wild-type mice. Similar results were observed in mice treated with antagonistic anti-PD-1 mAb.

Conclusions: : Since blockade of PD-1 pathway exacerbated the development of EAU by promoting Th1 and Th17 immune responses, it was demonstrated that PD-1 pathway plays a critical role in regulating EAU.

Keywords: uveitis-clinical/animal model • immunomodulation/immunoregulation • inflammation 
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