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CD40-expressing Carcinoma Cells Induce Down-Regulation of CD40 Ligand (CD154) and Impair T-Cell Functions¹

Institute of Immunology [R. B., M. L.], and Division of Urology of the Department of Surgery [W. R.], University of Heidelberg, 69120 Heidelberg; Department of Obstetrics and Gynecology, University of Heidelberg, 69115 Heidelberg [S. S.]; and University of Tübingen, 72076 Tübingen, [D. W., B. G.] Germany

The interaction of CD40 expressed by immunocompetent cells with its ligand CD154 on the surface of T-helper cells plays a crucial role in the immune response. Recently, the presence of CD40 was also demonstrated on a variety of carcinomas. Whereas the critical relevance of CD40 in cytotoxic T-cell priming via dendritic cells is already established, the biological role of CD40/CD154 interactions in nonhematopoetic cells is still unclear. In the present study we demonstrate that CD154 expression density is down-regulated on activated T cells on interaction with CD40⁺ tumor cells. Naive T cells cocultured with CD40⁺carcinoma showed impaired functionality as indicated by a reduced frequency of IFN- secreting cells, reduced interleukin 2 secretion, impaired proliferation, and a lack of CD154 re-expression on restimulation. In distinction, T-cell effector lysing capacity was not impaired by CD40-expressing tumor cell targets. The present results suggest that in marked contrast to antigen-presenting cells, CD40 expression on carcinoma cells suppresses T-cell activation. Our findings support the statement that CD40 functions are context dependent and imply a new function for CD40 expressed on nonantigen-presenting cells.

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