CD28 and CD27 costimulation of CD8+ T cells: a story of survival.

Although the requirement of CD28 and CD27 costimulation has been clearly demonstrated during primary CD8+ T cell responses and this costimulation acts by providing proliferation and survival cues to naive CD8+ T cells, a number of questions also arise from these studies. Is the requirement for CD28 and CD27 costimulation restricted to the initiation of the immune response in the lymph nodes, where presumably the initial contact between naive CD8+ T cell and DC occurs? What is the purpose of the dramatic influx of DC to sites of inflammation such as the lung during influenza virus infection and the formation of inflammatory BALT (iBALT)?(104) Are such DC at the site of inflammation and at later stages of the immune response providing cytokines or costimulation to effector CD8+ T cells? If DC are required for optimal secondary responses (100), is CD28 costimulation the missing signal or is it other members of the B7:CD28 family or TNF family? Given that a number of investigators are actively addressing these questions, the answers we expect will be soon to come and open exciting new opportunities for immune enhancement or dampening strategies and vaccine adjuvants.