CD40 as a mediator of proliferation in normal ans neoplastic thymic epithelium

AIMS AND METHODS: While CD40 is a costimulatory molecule of utmost importance for B-cell proliferation and Ig class switch its role has not been elucidated in the human thymus and in thymic epithelial tumors. To investigate, whether CD40 is functionally active there, we investigated the proliferative response by 3H-Thymidin incorporation of primary normal and neoplastic thymic epithelial cell cultures to CD40 triggering by soluble CD40 ligand (CD40L). RESULTS: Normal thymic epithelial cells exhibited proliferation in response to CD40 ligand in a dose dependent manner, while a CD40 ligand specific monoclonal antibody prevented this effect. This response was not significantly different from the response of neoplastic thymic epithelial cells derived from myasthenia gravis-associated thymomas. CONCLUSION: Our data demonstrate that CD40 is expressed on the surface of normal and neoplastic epithelial cells of the thymus and is a functional molecule in terms of epithelial cell proliferation in vitro. Given the differential expression of CD40 in the various histological thymoma subtypes in vivo, the finding suggests a role of CD40 in the different mechanisms of tolerance breakdown in thymomas.