FIG. 2.

One current model focuses on TED being triggered by activation of orbital fibroblasts by autoantibodies. These autoantibodies could be specific for antigens such as TSH-R and/or IGF-1R. Activated orbital fibroblasts release chemokines, including IL-16 and RANTES, which traffic T cells into the orbit. These lymphocytes then interact with fibroblasts, potentially activating each other, further promoting cytokine production (IFNγ, PGD₂, and 15d-PGJ₂) and secretion of T cell-activating factors by the fibroblasts (IL-1α, IL-8, and products of Cox-2 activity). Fibroblasts are also stimulated to secrete IL-6, which stimulates B cell differentiation. The interactions of fibroblasts with T cells result in the deposition of extracellular matrix molecules, fibroblast proliferation, and differentiation.