Type-1 polarized nature of mouse liver CD8alpha- and CD8alpha+ dendritic cells: tissue-dependent differences offset CD8alpha-related dendritic cell heterogeneity.
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 CD8alpha+ and CD8alpha- DC that show strong differences in their respective IL-12p70-producing capacities, CD8alpha+ and CD8alpha- DC isolated from the liver, a non-lymphoid organ, both efficiently produce IL-12p70 in amounts comparable to spleen CD8alpha+ DC. The IL-12p70-producing capacity CD8alpha+ and CD8alpha- 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 CDalpha8- 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.
O'Connell
Peta J
PJ
Department of Surgery, University of Pittsburgh, Hillman Cancer Center Research Pavilion, 5117 Centre Avenue, Pittsburgh, PA 15213-1863, USA.
Son
Young-Ik
YI
Giermasz
Adam
A
Wang
Zhiliang
Z
Logar
Alison J
AJ
Thomson
Angus W
AW
Kalinski
Pawel
P
D000818:Animals; D016827:CD8 Antigens / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009928:Organ Specificity / Q000502:physiology*; D013154:Spleen / Q000378:metabolism
D016827:CD8 Antigens; D018664:Interleukin-12