Role of Costimulation in the Induction of the IL-12/IL-12 Receptor Pathway and the Development of Autoimmunity

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Abstract
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 response and may influence Th1/Th2 development. The IL-12Rβ2 subunit plays 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 of the IL-12Rβ2 subunit and as a result the differentiation of pathogenic autoreactive effector cells. These findings suggest that targeting IL-2 and IL-12 simultaneously may be effective in the treatment of Th1-mediated autoimmunity.