1. Accessory cells precondition naïve T cells and regulatory T cells for cytokine-mediated proliferation.
- Author
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Sato, Noriko, Bamford, Richard N., Bryant, Bonita R., Yutaka Tagaya, and Waldmann, Thomas A.
- Subjects
REGULATORY T cells ,ANTIGEN presenting cells ,T cell receptors ,T cells ,CELL proliferation - Abstract
Naïve T cells and regulatory T cells, when purified, do not proliferate to the γc-cytokines IL-2, IL-7, or IL-15, despite their expression of cognate cytokine receptors. Dendritic cells (DCs) enabled the T cell proliferation to these cytokines, through cell-to-cell contact, but independent of T cell receptor stimulation. This effect lasted after separation of T cells from DCs, enabling enhanced proliferation of the T cells in DC-depleted hosts. 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. Collectively, accessory cells provide T cell preconditioning, a unique activation mechanism, controlling cytokine-mediated proliferation of T cells. [ABSTRACT FROM AUTHOR]- Published
- 2023
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