T Cell Help Amplifies Innate Signals in CD8+ DCs for Optimal CD8+ T Cell Priming

Marie Greyer, Paul G Whitney, Angus T. Stock, Gayle M. Davey, Christina Tebartz, Annabell Bachem, Justine D. Mintern, Richard A Strugnell, Stephen J. Turner, Thomas Gebhardt, Meredith O'Keeffe, William R Heath, Sammy Bedoui

Research output: Contribution to journalArticleResearchpeer-review

28 Citations (Scopus)

Abstract

DCs often require stimulation from CD4+ T cells to propagate CD8+ T cell responses, but precisely how T cell help optimizes the priming capacity of DCs and why this appears to differ between varying types of CD8+ T cell immunity remains unclear. We show that CD8+ T cell priming upon HSV-1 skin infection depended on DCs receiving stimulation from both IFN-α/β and CD4+ T cells to provide IL-15. This was not an additive effect but resulted from CD4+ T cells amplifying DC production of IL-15 in response to IFN-α/β. We also observed that increased innate stimulation reversed the helper dependence of CD8+ T cell priming and that the innate stimulus, rather than the CD4+ T cells themselves, determined how "help'" was integrated into the priming response by DCs. These findings identify T cell help as a flexible means to amplify varying suboptimal innate signals in DCs.

Original languageEnglish
Pages (from-to)586-597
Number of pages12
JournalCell Reports
Volume14
Issue number3
DOIs
Publication statusPublished - 26 Jan 2016

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