Modification of accessory molecule signaling

The concept of costimulation, the requirement for an independent accessory cellular activation signal that supplements the signal delivered to a lymphocyte by antigen, has been a focal point of progress in understanding the regulation of the immune system. While considerable attention has been directed to new developments related to the activation of cells of the innate immune system through Toll-like receptors, resulting in the production of soluble mediators, augmented expression of cell surface costimulatory molecules on antigen-presenting cells is arguably the most significant early outcome of immune system activation. It is those cell surface molecules that provide the essential afferent costimulatory signals to T cells of the adaptive immune response. Once fully activated, T cells express their own cell surface accessory molecules that permit those T cells to instruct interacting B cells, macrophages, and dendritic cells to further implement an effective immune response. Significantly for patients with autoimmune diseases, the manipulation of costimulatory signals represents a rational and effective approach to modulating the chronic immune system activation that characterizes those diseases. Further elucidation of the complexities of members of the accessory molecule families and their functions should lead to an ever greater capacity for therapeutic modulation of the immune response in autoimmune and inflammatory diseases.