Accessory cells precondition naive T cells and regulatory T cells for cytokine-mediated proliferation

Abstract Naïve T cells and regulatory cells, when purified, do not proliferate to the common cytokine receptor γ-chain family cytokines interleukin (IL)-2, IL-7 or IL-15, despite their expression of cognate receptors. Cell-to-cell contact with dendritic (DCs) enabled proliferation cell these cytokines, independent antigen recognition stimulation. This effect lasted after separation from DCs, enabling enhanced in mice depleted DCs. We propose calling this a “preconditioning effect”. Interestingly, IL-2 alone was sufficient induce phosphorylation nuclear translocation STAT5 but could activate MAPK AKT pathways failed transcription IL-2-target genes. Preconditioning necessary two pathways, induced weak Ca 2+mobilization calcium release-activated channels. When preconditioning combined IL-2, full activation downstream mTOR, 4E-BP1 hyperphosphorylation prolonged S6 occurred, underwent proliferation. Collectively, accessory provide preconditioning, unique mechanism, controlling cytokine-mediated cells.