Differential requirement of CD28 for IL-12 receptor expression and function in CD4+ and CD8+ T cells

Abstract

IL-12 is a potent inducer of IFN-γ production and Th1 responses. Co-stimulation mediated by B7 has been shown to synergize with IL-12 for optimal IFN-γ production and proliferation in vitro. In this study, we examined the requirement of CD28/B7 interactions for optimal induction of IL-12 receptor(R) β1 and β2 expression and IFN-γ. IL-12-induced IFN-γ production and STAT4 nuclear translocation were markedly reduced in CD28-/- splenocytes compared to that of wild-type (WT) splenocytes. Analysis of IL-12R expression revealed that IL-12 induced similar levels of IL-12R β2 mRNA expression in WT and CD28-/- cells. In contrast, IL-12R β1 expression was impaired in CD28-/- cells, indicating that expression of IL-12R β1 and β2 is differentially regulated by CD28. CD28-/- CD4+ but not CD8+ cells exhibited a defect in IL-12Rβ1 expression that was associated with a marked decrease in IL-12 binding as well as IL-12-induced IFN-γ production. IL-2 could restore IL-12R expression to CD28-/- CD4+ cells, however, this occurred independently of IL-2-induced proliferation. Thus, these findings identify distinct requirements for CD28 in the capacity of CD4+ and CD8+ cells to respond maximally to IL-12.