Type-1 polarized nature of mouse liver CDα- and CD8α+ dendritic cells: Tissue-dependent differences offset CD8α-related dendritic cell heterogeneity

Abstract

Interleukin-12 p70 (IL-12p70) is a major dendritic cell (DC)-produced cytokine known to support type-1 T helper (Th1) cells and inflammatory-type immunity. While the ability of DC to produce bioactive IL-12p70 depends on both the DC subtype and the microenvironmental conditions of DC development, the relative contribution of each of these factors remains unclear. Here, we report that in contrast to spleen CD8α+ and CD8α- DC that show strong differences in their respective IL-12p70-producing capacities, CD8α+ and CD8α- DC isolated from the liver, a non-lymphoid organ, both efficiently produce IL-12p70 in amounts comparable to spleen CD8α+ DC. The IL-12p70-producing capacity of CD8α+ and CD8α- DC from either location is greatly increased following their overnight culture in the presence of granulocyte-macrophage colony-stimulating factor. The elevated production of IL-12p70 by short-term cultured DC correlates with their enhanced expression of CD40 and other costimulatory molecules, and elevated T cell-stimulatory capacity. These data indicate that low IL-12-producing capacity is not an intrinsic property of the CD8α- DC subtype, and support the hypothesis that factors such as the site of DC development and maturation stage play a dominant role in defining DC function.