RETROBULBAR T-CELLS FROM PATIENTS WITH GRAVES OPHTHALMOPATHY ARE CD8+AND SPECIFICALLY RECOGNIZE AUTOLOGOUS FIBROBLASTS

Graves' ophthalmopathy is an autoimmune condition characterized by T c ell infiltration of the retrobulbar tissue. Phenotypic and functional analysis of these infiltrating cells may provide insight into the path ogenesis of the disease. IL-2-responsive cells were therefore grown ou t of the retrobulbar tissue from two patients with severe Graves' opht halmopathy undergoing orbital decompression surgery, and sis T cell li nes were established and characterized. They consisted predominantly o f CD8(+)CD45RO(+) cells and secreted IL-4, IFN-gamma, and IL-10 upon a ctivation. When screened for their antigen reactivity, all lines proli ferated in response to stimulation with autologous retrobulbar fibrobl asts in an HLA class I-restricted manner, but did not recognize autolo gous peripheral blood mononuclear cells, crude eye muscle extract, all ogeneic cells, or purified protein derivate of Mycobacterium tuberculo sis. In contrast, PBMC from the same patients responded readily to pur ified protein derivate of Mycobacterium tuberculosis and allogeneic PB MC, but did not recognize autologous fibroblasts. Interestingly, only one of the six retrobulbar T cell lines displayed cytotoxicity towards its specific target cell population. These results suggest that the r etrobulbar fibroblasts are a major T cell target in Graves' ophthalmop athg. Pronounced cytokine production in the absence of target cell cyt otoxicity may explain fibroblast proliferation. glycosaminoglycan secr etion, and secondary eye muscle enlargement in this condition.