Inflammatory cytokines provide a third signal for activation of naive CD4⁺ and CD8⁺ T cells

The effects of inflammatory cytokines on naive T cells have been studied using MHC protein/peptide complexes on microspheres, thus avoiding the use of APCs whose functions may be affected by the cytokines. IL-1, but not IL-12, increased proliferation of CD4⁺ T cells in response to Ag and IL-2, which is consistent with effects on in vivo priming of CD4⁺ cells. In contrast, proliferation of CD8⁺ T cells to Ag and IL-2 required IL-12, and IL-12 replaced adjuvant in stimulating an in vivo response to peptide. These results support a model in which distinct inflammatory cytokines act directly on naive CD4⁺ and CD8⁺ T cells to provide a third signal, along with Ag and IL-2, to optimally activate differentiation and clonal expansion.