CD40 is a 40 kDa type I glucoprotein membre of the nerve growth factor receptor/tumour necrosis factor family. It is found on numerous types of cells including B lymphocytes, dendritic and follicular dendritic cells, macrophages, haematopoietic progenitors, endothelial and epithelial cells, fibroblasts and carcinoma cells.
Interaction with its ligand (CD40L, a type II membrane protein of 33 kDa and a member of the tumour necrosis factor gene family) results in potent activation and survival stimuli. These include the production of various cytokines (e.g. GM-CSF, IL-1, IL-4, IL-6, IL-8, IL-10, IL-12, RANTES, TNFα) and up-regulation of adhesion and costimulatory molecules (ICAM-1, CD23, CD62E, CD80, CD86, CD106, etc.).
Upon activation, CD40 is transiently expressed on the surface of CD4+ and CD8+ lymphocytes, mast cells, NK cells and γ δ T lymphocytes. Later it is rapidly shed in the supernatant in trimeric form where it retains its full biological activity. Furthermore, CD40L is expressed on resting T lymphocytes at a minimal but sufficient level to exert a biological effect.
CD40 delivers potent co-stimulatory signals to effector cells through CD40L and has been suggested to be responsible for the initiation of immune responses. Co-immunisation with CD40L markedly enhances antibody and CTL-mediated immune responses.