title: CD40 expression in human thyroid tissue: evidence for involvement of multiple cell types in autoimmune and neoplastic diseases.
abstract: CD40, a member of the tumor necrosis factor-alpha (TNF-alpha) receptor family of surface molecules, is expressed by a variety of cell types. It is a crucial activational molecule displayed by lymphocytes and other bone marrow-derived cells and recently has also been found on nonlymphoid cells such as fibroblasts, endothelia, and epithelial cells in culture. While its role in lymphocyte signaling and activation has been examined in great detail, the function of CD40 expression on nonlymphoid cells, especially in vivo, is not yet understood. Most of the studies thus far have been conducted in cell culture. In this article, we report that several cell types resident in thyroid tissue in vivo can display CD40 under pathological conditions. Sections 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 carcinoma. Thyroid epithelial cells, lymphocytes, macrophages, endothelial cells, and spindle-shape fibroblast-like cells were found to stain positively in the context of inflammation. The staining pattern observed in all cell types was entirely membranous. In general, epithelial staining was limited to that adjacent to lymphocytic infiltration except in 5 of 17 cases of neoplasia and in diffuse hyperplasia. Moreover, we were able to detect CD40 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR) in human thyroid tissue. These results constitute convincing evidence for expression of CD40 in nonlymphocytic elements of the human thyroid gland. Our findings suggest a potentially important pathway that might be of relevance to the pathogenesis of thyroid diseases. They imply the potential participation of the CD40/CD40 ligand bridge in the cross-talk between resident thyroid cells and bone marrow-derived cells recruited to the thyroid.
authors.affiliation: Department of Medicine, Albany Medical College and Samuel S. Stratton Veterans Affairs Medical Center, New York 12208, USA. terry_j._smith@ccgateway.amc.edu
authors.forename: T J
authors.initials: TJ
authors.lastname: Smith
authors.forename: D
authors.initials: D
authors.lastname: Sciaky
authors.forename: R P
authors.initials: RP
authors.lastname: Phipps
authors.forename: T A
authors.initials: TA
authors.lastname: Jennings
mesh_terms: D019013:CD40 Antigens / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013961:Thyroid Gland / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013965:Thyroidectomy; D013967:Thyroiditis, Autoimmune / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D019013:CD40 Antigens; D012333:RNA, Messenger