T-CELL INTERACTIONS WITH EXTRACELLULAR-MATRIX PROTEINS IN PATIENTS WITH THYROID-ASSOCIATED OPHTHALMOPATHY

Although thyroid-associated ophthalmopathy (TAO) is now generally acce pted as an autoimmune inflammatory disorder of the extraocular muscles and the orbital connective tissue, its aetiopathogenesis remains poor ly understood. Recent data indicate that impaired interactions between T cells and extracellular matrix (ECM) proteins may play an important role in development and maintaining of an inflammatory process. We re port here results of the study focusing on interactions between T lymp hocytes and collagen-I (Coll-I), collagen-IV (doll-IV), fibronectin (F N), laminin (LM) in patients with TAO. Using a standard peripheral blo od mononuclear cells (PBMC) proliferation assay, we observed a markedl y enhanced T cell response to Coll-I in patients with active TAO (mean SI = 4.5). The proliferatory response to Coll-I was significantly gre ater (Wilcoxon test; p < 0.001) than in normal subjects (mean SI = 1.8 8), patients with stable TAO (mean SI = 2.05) and patients with thyroi d autoimmune diseases (AITD) without ophthalmopathy (mean SI = 2.49), PBMC stimulation by Coll-I is likely to be antigen-dependent requiring engagement of the T cell receptor with collagen peptides, rather than mediated via integrins. The percentage of circulating CD29(+) (beta 1 integrin chain) T cells war; not increased in patients with active TA O. Additionally in the assay of costimulation of CD3-mediated prolifer ation, we found that peripheral blood T cells from patients with TAO a nd AITD were costimulated only by FN, On the other hand a markedly enh anced costimulation of CD3-mediated proliferative responses by Coll-I, Coll-IV, FN and LM were observed in a retrobulbar T cell line. We con clude that abnormalities in T cell interactions with ECM proteins, esp ecially Coll-I may play a role in the pathogenesis of TAO.