RETROBULBAR FIBROBLASTS FROM PATIENTS WITH CRAVES OPHTHALMOPATHY INDUCE DOWN-REGULATION OF APO-1 IN T-LYMPHOCYTES AND PROTECT T-CELLS FROM APOPTOSIS DURING COCULTURE

Retrobulbar fibroblasts are a main target of the immune process in Gra ves' ophthalmopathy (GO) and have been shown to have unique metabolic qualities. The aim of our study was to analyze the immunoregulatory pr operties of retrobulbar fibroblasts and particularly whether fibroblas ts were able to protect T cells from apoptosis. Retrobulbar fibroblast s from patients with GO spontaneously expressed higher concentrations of HLA class I and HLA class II (p<0.05) than control cells, whereas b asal CD54 expression was unimpaired. Stimulation with IFN gamma led to a more pronounced increase in HLA class I, class II and CD54 in autoi mmune fibroblasts than in control cells (p<0.05). Fibroblasts from bot h groups had the capacity to prevent apoptosis in preactivated periphe ral T cells during coculture. T cell survival was, however, more prono unced after coculture with retrobulbar fibroblasts than with control c ells (p<0.05). Prevention of T cell death was associated with a decrea sed expression of APO-1 on the T cell surface, whereas the bcl-2 expre ssion of the T cells remained unchanged. Our results suggest that the increased expression of immunoregulatory molecules combined with a pro nounced capacity of autoimmune fibroblasts to protect infiltrating T c ells from apoptosis might at least partly explain the site selectivity as well as the perpetuation of the extrathyroidal manifestation of Gr aves' disease.