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

Abstract

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