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Supplementation of CD4+CD25+ regulatory T cells suppresses experimental autoimmune uveoretinitis
  1. H Keino,
  2. M Takeuchi,
  3. Y Usui,
  4. T Hattori,
  5. N Yamakawa,
  6. T Kezuka,
  7. J-I Sakai,
  8. M Usui
  1. Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan
  1. Correspondence to: Dr M Takeuchi Department of Ophthalmology, Tokyo Medical University, 6-7-1, Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan; takeuchi{at}tokyo-med.ac.jp

Abstract

Aims: To investigate whether supplementation of natural CD4+CD25+ regulatory T cells ameliorates mouse experimental autoimmune uveoretinitis (EAU) induced by CD4+ T cell-dependent interphotoreceptor retinoid-binding protein (IRBP).

Methods: C57BL/6 mice were immunised with human interphotoreceptor retinoid-binding protein peptide 1–20 (IRBP1–20), and IRBP1–20-sensitised T cells were obtained. CD4+CD25+ T cells derived from naive mice were cocultured with IRBP1–20-sensitised T cells, and their proliferation responses and cytokine production were measured. In addition, CD4+CD25+ T cells were transferred intravenously into mice 7 or 15 days after immunisation with IRBP1–20, and the severity of EAU and T cell proliferation responses were evaluated.

Results: CD4+CD25+ regulatory T cells effectively inhibited both the proliferation of, and interleukin (IL)2, IL5 and interferon (IFN)γ production by, IRBP1–20-sensitised T cells. Adoptive transfer of CD4+CD25+ regulatory T cells to IRBP1–20-immunised mice conferred considerable protection from EAU development and inhibition of T cell proliferation responses to IRBP1–20.

Conclusion: These findings show that natural CD4+CD25+ regulatory T cells possess the ability to inhibit activation of IRBP-reactive T cells that have been already sensitised in vivo, and adoptive transfer of these cells ameliorates EAU even in the effector phase. Supplementation of natural CD4+CD25+ regulatory T cells may have therapeutic potential for effective treatment of uveitis.

  • CFA, complete Freund’s adjuvant
  • EAU, experimental autoimmune uveoretinitis
  • IFN, interferon
  • IRBP, interphotoreceptor retinoid-binding protein
  • IRBP1–20, interphotoreceptor retinoid-binding protein peptide 1–20
  • PCR, polymerase chain reaction
  • TCR, T cell receptor
  • TGF, transforming growth factor

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Footnotes

  • Published Online First 30 August 2006

  • Funding: This work was supported by Grant-in-Aid 17791258 for Scientific Research from the Japan Society for the Promotion of Science.

  • Competing interests: None declared.

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