Suppressor role of rat CD8+CD45RClow T cells in experimental autoimmune uveitis (EAU)

To determine whether decreased regulatory T cell activity contributes to the pathogenesis of recurrent experimental autoimmune uveitis (EAU), we compared the immunoregulatory activity of CD8(+)CD45RC(low) T cells isolated from rats that had recovered from acute EAU with those from rats with the progressive, recurrent disease. Our results showed that 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-gamma by autoreactive T cells. Our data indicate that the decreased suppressive activity of CD8(+)CD45RC(low) T cells is correlated with disease development in this autoimmune disease. Further studies on the biology of this T cell population should provide much needed insights into disease pathogenesis. (c) 2006 Elsevier B.V. All rights reserved.