Viral dsRNA-activated human dendritic cells produce IL-27, which selectively promotes cytotoxicity in naive CD8+ T cells.

Abstract

Viral recognition programs DCs to express Signal 3 molecules that promote the differentiation of effector CD8(+) T cells. Besides IL-12, another DC-derived IL-12 family member, IL-27, has been reported to contribute herein, but its specific role is not well understood. Here, we show that whereas IL-12 potently induces inflammatory cytokines (i.e., IFN-gamma and TNF-alpha, but not IL-2), IL-27 excels in inducing proliferation and a cytotoxic profile (GrB, cytotoxicity of target cells) in human naive CD8(+) T cells. Compared with bacterial cell-wall peptidoglycan, viral dsRNA-mimic poly (I:C) is superior in priming human BDCA1(+) peripheral blood DCs to produce IL-12 and IL-27, which promote inflammatory cytokines and a cytotoxic profile in differentiating CD8(+) T cells, respectively. These data support the concept that viral dsRNA-activated human DCs produce IL-27 to act as a specialized procytotoxic, antiviral cytokine in the development of effector CD8(+) T cells.