Distribution of molecules mediating thymocyte-stroma-interactions in human thymus, thymitis and thymic epithelial tumors.
Two findings in thymic epithelial tumors are correlated with the occurrence of myasthenia gravis(MG): (1) the expression of an acetylcholine receptor (AChR)-like-epitope in the neoplastic epithelium, and (2) the preservation of thymus-like features in the neoplasms, indicated by the presence of immature thymocytes. On this background it has been proposed that paraneoplastic MG may start with an intratumorous abnormal T cell selection due to aberrantly expressed AChR-epitopes (self-peptides). As appropriate thymocyte-stroma-interactions are prerequisites for thymocyte development in the thymus (and probably in MG-associated thymic tumors, too), we analyzed the expression of CD28/B7(BB1), CD2/:LFA3, LFA-1/ICAM-1 and VLA-4/VCAM-1 in human thymus and thymomas by immunohistochemistry. In normal thymuses and thymitis the stromal molecules were expressed at higher levels in the medulla than in the cortex. This was particularly true for B7(BB1) that was undetectable by immunoperoxidase techniques in the cortex. In contrast, cortical-type thymic epithelial tumors (cortical thymoma and well differentiated thymic carcinoma), known to exhibit the highest association with myasthenia, expressed the stromal molecules at almost medullary levels. The findings may be a clue to a functional difference between neoplastic and normal cortical epithelial cells: while we find the former to have the capacity to present soluble antigen to antigen-specific CD4+ T cells in vitro, normal cortical epithelium failed to do so. This altered microenvironment in thymomas might contribute to the autoimmunization by stimulating mature recirculating AChR-specific T cells.
Marx
A
A
Institutes of Pathology, University of Würzburg, Germany.
Schömig
D
D
Schultz
A
A
Gattenlöhner
S
S
Jung
A
A
Kirchner
T
T
Melms
A
A
Müller-Hermelink
H K
HK
D018801:CD2 Antigens; D018106:CD28 Antigens; D002454:Cell Differentiation; D004848:Epithelium / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1; D008206:Lymphatic Diseases / Q000378:metabolism / Q000473:pathology; D009157:Myasthenia Gravis / Q000150:complications; D011950:Receptors, Cholinergic / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology; D013945:Thymoma / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000378:metabolism* / Q000648:ultrastructure; D013953:Thymus Neoplasms / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018801:CD2 Antigens; D018106:CD28 Antigens; D011950:Receptors, Cholinergic; D018799:Intercellular Adhesion Molecule-1