The Concept of Co-Stimulatory Blockade in SLEplease remove Aff4

The beautifully orchestrated inflammatory cascade in response to a threat relies on an important mechanism called co-stimulation that occurs between the antigen presenting cells and T cells. Our understanding of how costimulatory molecules play a role in lupus pathogenesis will create novel ways to damper the inflammatory cascade and promote immune tolerance. The best-studied costimulatory molecules in SLE are the CD28/B7 system utilising CTLA4Ig to damper down the T cell response, but many more are of pertinent interest to downregulate the adaptive T-cell dependent humoral response. For example, the ICOS/ICOSL, CD40L/CD40, and PD1/PDL1 pathways are all relevant co-stimulatory molecules that are susceptible to manipulation, with the end-result on activation and maintenance of germinal centre response and production of high affinity autoantibodies. In this chapter, the biology of these costimulatory molecules will be summarised and the data supportive of them as emerging therapeutic targets in the SLE discussed.