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

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.