The~'namic and reciprocal communication between T helper (Tb) cells and B cells appears to rely on the provision of multiple signals. The first is antigen specific and is mediated by the interaction between the T-cell receptor (TCR) and antigen bound to the major histocompatibility complex"(MHC). The subsequent signals are provided by the binding of accessor 3'molecules such as CD28 and CD40 to their respective ligands. Here, Fiona Durie and colleagues discuss the co-stimulatory role of the interaction between CD40 on B cells and CD40 ligand (CD4OL, gp39) on T cells, and review e,, idence that sug, eests blocking this interaction may induce T-celi tolerance.

Recognition of processed antigen on the surface of the antigen-presenting B cell by the T-cell receptor (TCR) represents the initial antigen-specific event leading to cog, l~ ate interactions. This recognition triggers the engagement of a series of accessory molecules, whose function is to stabilize the interaction and to coordinate the responses of the interacting cells. In general, the accessory molecules enter the communication process either bv increasing their cellsurface density [eg B7 and CD40 iigand (CD40L, gp39)](Refs 1-4) or by changing their affinity for ligand [eg lymphocyte function-assoclated molecule 1 (LFA-1)](Ref. 5). Two ligand-receptor systems that exert profound influences on the outcome of cognate interactions have been identified recently. First, the ligation of CD28/CTLA-4 on the T cell to B7. 1 and B7. 2 on the B cell signals the TCR-activated T cell to produce lymphokines and avoid anergv 3, 6-9. Efficient ligation of CD28/CTLA-4 is attained by the upregulation of B7. 1 and B7. 2 densities on the antigen-presenting cell (APC)(Refs 3, 4). Second, the expression of CD40L by activated T helper (Th) cells triggers B-cell cycling through binding to CD40 (Refs 1, 10, 11). Efficient triggering of B cells is afforded by increasing the density of CD40L on the T-cell surface 1, 2.12. Recent studies have investigated the interdependence of the expression and function of CD40L and B7 dur-