Switching off autoimmunity

Abstract

The ability to selectively switch off adaptive immunity presents a remarkable opportunity for therapeutic intervention in autoimmune disease. There is one molecule whose targeting will allow such unbridled control over disease, the cytokine CD40 ligand (CD40L). Transiently expressed on activated T cells, CD40L is essential for the development of antibody- and cell-mediated immune responses. For over 30 years, efforts to develop safe and effective therapeutic agents to disable the function of CD40L have been sought. Finally, that battle has been won. A number of CD40L antagonists have entered clinical trials and have demonstrated therapeutic benefit in organ-specific and systemic autoimmune diseases. The use of CD40L antagonists will expand to a wider spectrum of human immune–mediated inflammatory diseases such as inflammatory bowel disease and rheumatoid arthritis owing to the newfound ability to control disease progression.