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 occur rence of myasthenia gravis(MG): (I) the expression of an acetylcholine receptor (AChR)-like-epitope in the neoplastic epithelium, and (2) th e preservation of thymus-like features in the neoplasms, indicated by the presence of immature thymocytes. On this background it has been pr oposed that paraneoplastic MG may start with an intratumorous abnormal T cell selection due to aberrantly expressed AChR-epitopes (self-pept ides). 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 im munohistochemistry. In normal thymuses and thymitis the stromal molecu les were expressed at higher levels in the medulla than in the cortex. This was particulrly true for B7(BB1) that was undetectable by immuno peroxidase techniques in the cortex. In contrast, cortical-type thymic epithelial tumors (cortical thymoma and well differentited thymic car cinoma), known to exhibit the highest association with myasthenia, exp ressed 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 capac ity to present soluble antigen to antigen-specific CD4(+) T cells in v itro, normal cortical epithelium failed to do so. This altered microen vironment in thymomas might contribute to autoimmunization by stimulat ing mature recirculating AChR-specific T cells.