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

• IFN-α/β and CD4+ T cells cooperate in enabling CD8+ DCs to provide IL-15
• Innate circuit stimulation determines cytokine requirements of CTL priming
• T cell help for CD8+ T cell priming is a means to amplify innate circuits in DCs

SummaryDCs 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.

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