Expression And Significance Of Costimulatory Molecules In The Autoimmune Thyroid Diseases

Activation of T lymphocytes requires at least two signals for proliferation and cytokine secretion. The first signal is delivered through the interaction of the T cell receptor (TCR) with its antigen presented on major histocompatibility complex (MHC). The second or costimulatory signal, neither antigen-specific nor MHC-restricted, is delivered by cell surface molecules expressed by antigen presenting cells. In the absence of such costimulatory signal, cognate antigen recognition will result in inhibitory events, such as anergy or unresponsiveness to further stimulation, or apoptosis. Costimulatory molecules are divided into two categraies according to their structure, the Ig super-family and TNF/TNFR super-family. B7/CD28, ICOS/GL50,PD-1/PD-L1 belong to Ig super-family while CD40/CD40L, 4-BB/4-1BBL, Fas/FasL, OX40/OX40L belong to TNF/TNFR super-family. Among them, CD40/CD40L and B7-1/CD28 have been studied fully in both super-families.Graves' disease (GD) and Hashimoto thyroiditis (HT) are characterized as organ-specific autoimmune disease. The main features of GD are hyperthyroidism due to the activation of thyroid follicular cell through the combination of antibody of thyroid stimulating hormone (TSH) receptor and receptor of TSH on the surface of thyroid follicular cell (auto-antigen). HT are caused by infiltration of immunocompetent cells, production of thyroid specific auto-antigen, presence of thyroid auto-antigen specific T lymphocyte, and damages of follicular structure. The abnormal activation of T cells and abnormal expression of costimulatory molecules correlated closely with the development of autoimmune disease.Method: Immunohistochemistry was performed to detected expression ofCD40/CD40L, B7-1/CD28, GL50, CD4, and CDS in the tissue of GD and HT. Results: The staining results showed that expression levels of CD40 and B7-1 were slightly higher in the GD group than the thyroid adenoma group without statistic significance (p > 0.05). while expression levels of CD40L, CD28, GL50, CD4, and CD8 were significantly higher in the GD group than those of adenoma group (p < 0.01). Expression levels of CD40, B7-1/CD28, GL50, CD4, and CDS were significantly higher in the HT group than those of adenoma group (p < 0.01).But no significant difference was found between the two groupsin terms of CD40L expression (p > 0.05 ). Conclusion: Costimulatory signals mediatedby CD40/CD40L, B7-1/CD28, ICOS/GL50 and CD4+ T lymphocytes and CD8+ T lymphocytes are important factors during the process of GD and HT. So it is of great significance to the therapy of GD and HT through blocking such signals, which provide new ways to the treatment of GD, HT and other autoimmune diseases.