CD40 expression in human thyroid tissue: Evidence for involvement of multiple cell types in autoimmune and neoplastic diseases

CD40, a member of the tumor necrosis factor-alpha (TNF-alpha) receptor fami ly of surface molecules, is expressed by a variety of cell types. It is a c rucial activational molecule displayed by lymphocytes and other bone marrow -derived cells and recently has also been found on nonlymphoid cells such a s fibroblasts, endothelia, and epithelial cells in culture. Wile its role i n lymphocyte signaling and activation has been examined in great detail, th e function of CD40 expression on nonlymphoid cells, especially in vivo, is not yet understood. Most of the studies thus far have been conducted in cel l culture. In this article, we report that several cell types resident in t hyroid tissue in vivo can display CD40 under pathological conditions. Secti ons from a total, of 46 different cases were examined immunohistochemically and included nodular hyperplasia, chronic lymphocytic thyroiditis, diffuse hyperplasia, follicular neoplasia, papillary carcinoma, and medullary carc inoma. Thyroid epithelial cells, lymphocytes, macrophages, endothelial cell s, and spindle-shape fibroblast-like cells were found to stain positively i n the context of inflammation. The staining pattern observed in all cell ty pes was entirely membranous. In general, epithelial staining was limited to that adjacent to lymphocytic infiltration except in 5 of 17 cases of neopl asia and in diffuse hyperplasia. Moreover, we were able to detect CD40 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR) in human thyro id tissue. These results constitute convincing evidence for expression of C D40 in nonlymphocytic elements of the human thyroid gland. Our findings sug gest a potentially important pathway that might be of relevance to the path ogenesis of thyroid diseases. They imply the potential participation of the CD40/CD40 ligand bridge in the cross-talk between resident thyroid cells a nd bone marrow-derived cells recruited to the thyroid.