Role of costimulation in the induction of the IL-12/PL-12 receptor pathwayand the development of autoimmunity

Costimulation mediated by the interactions of the B7 Ags (CD80/CD86) on APC with CD28 on the responding T cell regulates the magnitude of the immune r esponse and may influence Th1/Th2 development. The IL-12R beta 2 subunit pl ays a critical role in maintaining IL-12 responsiveness and controlling Th1 lineage commitment. We demonstrate that IL-2 and IL-12 resulting from CD28 /B7 interactions both play a critical role in the induction of expression o f the IL-12R beta 2 subunit and as a result the differentiation of pathogen ic autoreactive effector cells. These findings suggest that targeting IL-2 and IL-12 simultaneously may be effective in the treatment of Th1-mediated autoimmunity.