Supplementation of Natural CD4+CD25+ Regulatory T Cells Sufficiently Suppresses Experimental Autoimmune Uveoretinitis

Abstract

Purpose: : The current study was designed to investigate whether supplementation of natural regulatory T cells ameliorates interphotoreceptor retinoid–binding protein (IRBP)–specific experimental autoimmune uveoretinitis (EAU).

Methods: : C57BL/6 mice were immunized in the neck with 200 microgram of human–IRBP peptide. Histopathological examination of EAU was assessed on days 21 after immunization. Cervical lymph node cells derived from mice immunized 14 days previously were cultured for 72 hours with CD4⁺CD25⁺ or CD4⁺CD25^– T cells isolated from naive mice. For delayed hypersensitivity (DH) assay, mice received an intradermal injection of 20 microgram of human–IRBP peptide into the right ear pinnae on day 20 after immunization. After 24 hours, the ear swelling was measured.

Results: : In vitro, natural CD4⁺CD25⁺ regulatory T cells effectively inhibited both the proliferation and Th1 cytokine production by draining lymph–node cells sensitized by human–IRBP peptide. In vivo, adoptive transfer of CD4⁺CD25⁺ regulatory T cells to immunized mice during the efferent phase conferred significant protection from development of EAU both clinically and histologically as well as human–IRBP peptide–specific DH response.

Conclusions: : These findings suggest that supplementation of natural CD4⁺CD25⁺ regulatory T cells may be an effective treatment for autoimmune uveitis

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