The critical role of CD40/CD40L in the CD4-dependent generation of CD8+ T cell immunity.

Control of virus infections and eradication of tumors usually involves the lytic activity of CD8+ cytotoxic T lymphocytes (CTLs). The induction of effective CTL immunity relies on several factors, one of the most important of which is CD4+ T cell help. Numerous studies have demonstrated the dependence of CTL priming on the presence of CD4+ T cells, but until recently little was known of the mechanisms regulating this process. Based on reports that CD4+ and CD8+ T cells must recognize antigen on the same antigen-presenting cell (APC), help was originally thought to be provided through the delivery of short-range, CD4+ T cell-secreted cytokines. However, the results of subsequent studies favor an alternative mechanism, whereby CD4+ T cells modify the APC, converting it into a stimulatory cell for CD8+ T cell priming. It is important that CD40 and its ligand, CD40L, have been implicated in the provision of this help and, in particular, the generation of long-lasting CTL memory.