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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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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