April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Immune Responses to Retina-Specific Antigens in Behçet's Patients With Uveitis
Author Affiliations & Notes
  • M. Takeuchi
    Ophthalmology, Tokyo Medical University, Shinjuku-Ku, Japan
  • Y. Usui
    Ophthalmology, Tokyo Medical University, Shinjuku-Ku, Japan
  • T. Hattori
    Ophthalmology, Tokyo Medical University, Shinjuku-Ku, Japan
  • Y. Okunuki
    Ophthalmology, Tokyo Medical University, Shinjuku-Ku, Japan
  • L. Zhang
    Ophthalmology, Tokyo Medical University, Shinjuku-Ku, Japan
  • N. Yamakawa
    Ophthalmology, Tokyo Medical University, Shinjuku-Ku, Japan
  • J. Ma
    Ophthalmology, Tokyo Medical University, Shinjuku-Ku, Japan
  • J.-I. Sakai
    Ophthalmology, Tokyo Medical University, Shinjuku-Ku, Japan
  • T. Kezuka
    Ophthalmology, Tokyo Medical University, Shinjuku-Ku, Japan
  • H. Goto
    Ophthalmology, Tokyo Medical University, Shinjuku-Ku, Japan
  • Footnotes
    Commercial Relationships  M. Takeuchi, None; Y. Usui, None; T. Hattori, None; Y. Okunuki, None; L. Zhang, None; N. Yamakawa, None; J. Ma, None; J.-I. Sakai, None; T. Kezuka, None; H. Goto, None.
  • Footnotes
    Support  Grant-in-Aid 16591769 for Scientific Research from the Japan Society for the Promotion of Science
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 6144. doi:
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    • Get Citation

      M. Takeuchi, Y. Usui, T. Hattori, Y. Okunuki, L. Zhang, N. Yamakawa, J. Ma, J.-I. Sakai, T. Kezuka, H. Goto; Immune Responses to Retina-Specific Antigens in Behçet's Patients With Uveitis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6144.

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

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Abstract

Purpose: : The role of autoimmune mechanisms in the pathogenesis of some human uveitic conditions has been suggested by in vitro studies demonstrating that lymphocytes from uveitic patients respond against retina-specific antigens that are uveitogenic in animals. It has also been shown that the majority of patients with uveitis associated with Behçet's disease (BD) respond to S antigen (S-Ag) and interphotoreceptor retinoid binding protein (IRBP), while some healthy subjects also respond to these antigens. In this study, we evaluated their immune responses to retina-specific antigens by examining the profile of cytokine production.

Methods: : Peripheral blood mononuclear cells (PBMCs) were collected from 32 BD patients with uveitis and 23 healthy subjects, and each sample was cultured for 48 hrs with 0, 1, 5 or 10 µg/ml of S-Ag or IRBP purified from swine retinae. At the end of culture, supernatants were collected, and IL-2, IL-4, IL-6, IL-10, IFN-γ and TNF- concentrations were measured by a cytometric bead array (CBA) kit using FACS and IL-17 concentration was determined by ELISA.

Results: : PBMCs from both BD patients and healthy subjects produced IL-6, IL-10, IL-17, IFN-γ and TNF- upon stimulation with S-Ag or IRBP in a dose-dependent manner, but did not produce IL-2 or IL-4. Both S-Ag- and IRBP-stimulated IL-6, IL-17, IFN-γ and TNF- productions were higher in BD patients than in healthy subjects but IL-10 production was not different between two groups. Especially, IRBP-stimulated IFN-γ production as well as S-Ag- and IRBP-stimulated IL-6 production were significantly higher in BD patients compared with healthy subjects. Interestingly, IFN-γ production was significantly higher when stimulated by IRBP than by S-Ag, whereas IL-6 production was significantly higher when stimulated by S-Ag than by IRBP.

Conclusions: : These results indicate that both S-Ag and IRBP act as retinal autoantigens, and suggest that IFN-γ-mediated immune response induced by IRBP and IL-6-mediated immune response induced preferably by S-Ag may play critical roles in the occurrence of ocular inflammation in Behçet's disease.

Keywords: uveitis-clinical/animal model • inflammation • immune tolerance/privilege 
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