Control of virus infections and eradication of tumors usually involves the
lytic activity of CD8(+) cytotoxic T lymphocytes (CTLs), The induction of e
ffective CTL immunity relies on several factors, one of the most important
of which is CD4(+) T cell help. Numerous studies have demonstrated the depe
ndence of CTL priming on the presence of CD4(+) T cells, but until recently
little was known of the mechanisms regulating this process. Based on repor
ts that CD4(+) and CD8(+) T cells must recognize antigen on the same antige
n-presenting cell (APC), help was originally thought to be provided through
the delivery of short-range, CD4(+) T cell-secreted cytokines, However, th
e 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 printing. It is important that CD40 and its ligand, CD40L, have be
en implicated in the provision of this help and, in particular, the generat
ion of long-lasting CTL memory.