Cees van Kooten and Jacques Banchereau

Dept of Nephrology, Leiden University Hospital, Leiden, the Netherlands and Schering-Plough, Laboratory for Immunological Research, Dardilly, France

Received 11/14/96; Accepted 12/02/96; On-line 01/01/97

4. CONCLUDING REMARKS

In recent years, the focus of CD40 research has been shifted from the study of B cell regulation (humoral immunity), to the study of a general regulator of immune and inflammatory processes. Especially the finding of CD40 expression on activated endothelium, has important clinical implications, as it places this molecule in the centre of (chronic) inflammation, transplantation, tumor metastasis, angiogenesis and normal leukocyte trafficking. Thus, multiple disease states appear to be improved by interruption of CD40/CD40-L interactions. This is presently accomplished by preventing the association of the receptor with its ligand using specific antibodies or soluble receptor molecules. However, for clinical applications, such reagents may not prove useful therapeutic entities. The identification of small synthetic chemical agents preventing the interaction of CD40 with its ligand would be of interest. Alternatively, by unravelling the signal transduction pathways of CD40 in different target cells, pharmacologic agents may be developed which will specifically block the intracellular pathways turned on after ligation of either CD40 or CD40-L. The recent identification of a dominant negative inhibitor of CD40 activation might represent a first step in this direction.