CD40 is a cell surface receptor that belongs to the tamar necrosis factor-I
l (TNF-R) family, and that was first identified and functionally characteri
zed on B lymphocytes, Its critical role in T cell-dependent humoral immune
responses was demonstrated by patients,vith the hyper-IgM syndrome, as well
as by gene targeting in mice. However, in recent years it has become dear
that CD40 is expressed much more Broadly, including expression on monocytes
, dendritic cells, endothelial cells, and epithelial cells. In addition, th
e CD40-ligand (CD40-L/CD154), a member of the TNF family, is also expressed
more widely than activated CD4(+) T cells only. Therefore it is now though
t that CD40-CD40-L interactions play a more general role in immune regulati
on. Collectively these studies have culminated in pre-clinical and clinical
studies that are in progress, This article reviews recent developments in
this field of research, with main emphasis on (T) structure and expression
of CD40 and its ligand; (2) CD40 signal transduction; (3) in vitro function
of CD40 on different cell types; and (4) in vivo functions of CD40/CD40-L
interactions.