Overexpression of CD40 on neoplastic epithelium has been found in most Myasthenia gravis (MG) associated thymoma. Whether CD40 is functionally expressed in thymoma and is involved in the generation of autoimmunity, has not been elucidated. To check the function of CD40, the proliferation of thymic epithelial cells (TEC) was induced by triggering the cells with soluble CD40 ligand. No difference between normal and neoplastic TEC was detected. IFN-γ could not modulate the CD40-dependent proliferation. In contrast IL-4 blocked the proliferative response of epithelial cells from normal thymus and cortical thymoma, but not from medullary thymoma. Since CD40/CD40 ligand interaction has been implicated in negative selection of immature T-cells, we compared the number of positively selected (immature) double positive CD69+ thymocytes with the number of (mature) single positive CD69+ cells, which are thought to have escaped negative selection. The ratio of mature to immature thymocytes was markedly reduced in thymoma. One explanation might be an enhanced deletion of positively selected thymocytes. Our results demonstrated, that CD40 is functionally expressed on normal and neoplastic epithelial cells in vitro. The data suggest, that maturation of autoaggressive T-cells in paraneoplastic MG is probably not caused by an unspecific inefficiency of negative selection.
KeywordsNegative Selection CD40 Ligand Thymic Carcinoma Thymic Epithelial Cell Normal Thymus
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