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 us ing 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, whi ch is consistent with effects on in vivo priming of CD4(+) cells, In contra st, proliferation of CD8(+) T cells to Ag and IL-2 required IL-12, and IL-1 2 replaced adjuvant in stimulating an in vivo response to peptide, These re sults support a model in which distinct inflammatory cytokines act directly on naive CD4(+) and CD8(+) T cells to provide a third signal, along with A g and IL-2, to optimally activate differentiation and clonal expansion.