Supplementation of CD4+CD25+ regulatory T cells suppresses experimental autoimmune uveoretinitis

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 (IRBP_1–20), and IRBP_1–20-sensitised T cells were obtained. CD4+CD25+ T cells derived from naive mice were cocultured with IRBP_1–20-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 IRBP_1–20, 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, IRBP_1–20-sensitised T cells. Adoptive transfer of CD4+CD25+ regulatory T cells to IRBP_1–20-immunised mice conferred considerable protection from EAU development and inhibition of T cell proliferation responses to IRBP_1–20.

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.