Suppressor Role of Rat CD8+CD45RClow T Cells in Experimental Autoimmune Uveitis (EAU)

Abstract

Purpose:: We have determined the role of CD8⁺CD45RC^low regulatory T cell activity in the pathogenesis of EAU.

Methods:: EAU was induced in Lewis rats either by immunization of IRBP1177-1191 (monophasic disease) or by injection of IRBP-specific T cells to Lewis rat (recurrent EAU). The CD8⁺CD45RC^low T cells were isolated from rat recovered from monophasic EAU or from rats in recurrent disease.

Results:: CD8⁺CD45RC^low T cells isolated from the recovered rats showed suppressive activity in vitro, whereas those from rats with progressive, recurrent EAU do not. Depletion of CD8⁺CD45RC^low T cells from T cells used for adoptive transfer of EAU increased the pathogenic activity of the T cells. Co-transfer of CD8⁺CD45RC^low T cells with uveitogenic T cells prevented the relapse of disease in the recipient rats. The suppressive CD8⁺CD45RC^low T cells expressed increased levels of Foxp3 after stimulation in vitro with the autoantigen, and inhibited the production of IFN-γ by autoreactive T cells.

Conclusions:: the decreased suppressive activity of CD8⁺CD45RC^low T cells is correlated with disease development in this autoimmune disease.Supported in part by NIH grants EY014-366, EY12974, EY14599 and the grant RG3413A4 from the National Multiple Sclerosis Society.

Keywords: autoimmune disease • uveitis-clinical/animal model