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We have previously demonstrated that thyrocytes from patients with Graves' disease induce autologous peripheral blood T cell proliferation in response to soluble antigens, and a synergistic augmentation of T cell response by adding suboptimal numbers of monocytes. In the present study, we examined the role of costimulatory molecules, expressed on the surface of thyrocytes and intrathyroidal mononuclear cells, in antigen-specific T cell proliferation. Intercellular associated molecule (ICAM)-1 and lymphocyte function associated antigen-3 were constitutively expressed on the surface of both normal and Graves' thyrocytes. However, ICAM-2, vascular cell adhesion molecule-1, B7-1, and B7-2 were not detected and induced by cytokines. B7-1, was expressed on intrathyroidal monocytes only, while B7-2 was present on intrathyroidal lymphocytes, peripheral blood monocytes, and intrathyroidal monocytes. Furthermore, the density of B7-2 was higher on intrathyroidal monocytes than on peripheral blood monocytes. The intensity of CD28 expression on intrathyroidal CD8bright+ cells was less than that on peripheral blood CD8bright+ cells. The antigen-specific T cell response induced by thyrocytes was blocked completely by anti-human leukocyte antigen-DR monoclonal antibody (mAb) and partially by anti-ICAM-1 mAb and anti-lymphocyte function associated antigen-3 mAb. Furthermore, the synergistic augmentation of T cell response, induced by the addition of suboptimal number of monocytes, was suppressed completely by combining anti-B7-1 mAb and anti-B7-2 mAb, to a level equivalent to that observed when thyrocytes were used alone as antigen-presenting cells. Our results suggest that T cell proliferation was induced by cooperation of thyrocytes and infiltrating professional antigen-presenting cells.

the journal of clinical endocrinology and metabolism/journal of clinical endocrinology and metabolism

Lack of B7-1/BB1 and B7-2/B70 expression on thyrocytes of patients with Graves' disease. Delivery of costimulatory signals from bystander professional antigen-presenting cells.