Science and medicine


CD40 is a member of the tumour necrosis factor receptor (TNF-R) related family.  Within the immune system, CD40 is expressed on several cell types including B-cells, macrophages, and dendritic cells. CD40 has a key function in B-cell activation and cellular viability.  It controls the lifespan of B-cells by preventing apoptosis following activation, is required for switching from IgM to IgG, IgA and IgE and for the affinity maturation of antibodies. The involvement in class switching is clearly illustrated by patients suffering from a dysfunctional CD40 ligand (CD154) resulting in the hyper-IgM syndrome.

CD40 also plays a role in the efficient activation of T-cells by antigen presenting cells (APCs).  The physiological ligand for CD40 is CD154. T-cell CD154 binding to CD40 on immature dendritic cells (DC) causes DC maturation, increases expression of the co-stimulatory molecules CD80 and CD86 on DCs, and causes increased production of cytokines, including TNF-α, interleukin 8 (IL-8) and IL-12, to be released from APCs.

CD40 may also be expressed on non-lymphoid cells, including endothelial cells, epithelial cells, fibroblasts, airway smooth muscle cells, neuronal cells, pancreatic beta cells, neutrophils and keratinocytes. CD40 expression is normally very low on most of these cells but may be induced at sites of inflammation. Stimulation by CD40 ligation results in increased cytokine and chemokine production, the expression of matrix metalloproteinases, tissue factor and adhesion molecules at the surface of the cells to promote leukocyte recruitment at the site of inflammation.

There is a wealth of literature strongly supporting the involvement of the CD154-CD40 interaction in the pathophysiology of a range of autoimmune diseases including lupus, rheumatoid arthritis, inflammatory bowel disorders and other B cell mediated autoimmune disorders. This conclusion reflects both animal models and clinical experience with antagonist antibodies in man. The CD40-CD154 interaction can be modulated with monoclonal antibodies against either CD154 or CD40.