Dendritic cells matured by inflammation induce CD86-dependent priming of naive CD8+ T cells in the absence of their cognate peptide antigen.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Asher MaroofPaul M Kaye

Abstract

Dendritic cells (DC) licensed by the interaction between pathogen products and pattern recognition receptors can activate naive T cells to undergo Ag-dependent proliferation and cytokine production. In contrast, DC induced to mature by trans-acting inflammatory stimuli are believed to only be capable of supporting Ag-dependent proliferative responses. In this study, we show that uninfected DC matured as a consequence of Leishmania-induced inflammation induce CD8(+) T cells to proliferate in the absence of their cognate Ag. We separated splenic DC from Leishmania donovani-infected mice into those that contained parasites and had been activated to induce IL-12p40, from those that had undergone only partial maturation, measured by increased CD86 expression in the absence of IL-12p40 induction. We then showed that these partially matured DC could induce exogenous peptide-independent proliferation of OT-I and F5 CD8(+) TCR transgenic T cells, as well as polyclonal CD8(+) T cells. Proliferation of OT-I cells was significantly inhibited in vitro and in vivo by anti-CD86 mAb but not by anti-CD80 mAb and could also be inhibited by cyclosporine A. Proliferating OT-I cells did not produce IFN-gamma, even when re-exposed to mature DC. Howe...Continue Reading

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Citations

Jul 9, 2011·Nature Immunology·Jonathan Sprent, Charles D Surh
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Jul 13, 2011·Nature Reviews. Microbiology·Paul Kaye, Phillip Scott
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Jul 23, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mohanraj RamachandranMagnus Essand

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