Differential Production of IL-12, IFN-α, and IFN-γ by Mouse Dendritic Cell Subsets

Journal of Immunology - Tập 166 Số 9 - Trang 5448-5455 - 2001
Hubertus Hochrein1,2, Ken Shortman1, David Vremec1, Bernadette Scott3, Paul J. Hertzog3, Meredith O’Keeffe1
1The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
2Institute of Medical Microbiology, Immunology and Hygiene, Technical University, Munich, Germany
3†Centre for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Clayton, Victoria, Australia; and

Tóm tắt

AbstractDendritic cells (DC) not only stimulate T cells effectively but are also producers of cytokines that have important immune regulatory functions. In this study we have extended information on the functional differences between DC subpopulations to include differences in the production of the major immune-directing cytokines IL-12, IFN-α, and IFN-γ. Splenic CD4−8+ DC were identified as the major IL-12 producers in response to microbiological or T cell stimuli when compared with splenic CD4−8− or CD4+8− DC; however, all three subsets of DC showed similar IL-12 regulation and responded with increased IL-12 p70 production if IL-4 was present during stimulation. High level CD8 expression also correlated with extent of IL-12 production for DC isolated from thymus and lymph nodes. By using gene knockout mice we ruled out any role for CD8α itself, or of priming by T cells, on the superior IL-12-producing capacity of the CD8+ DC. Additionally, CD8+ DC were identified as the major producers of IFN-α compared with the two CD8− DC subsets, a finding that suggests similarity to the human plasmacytoid DC lineage. In contrast, the CD4−8− DC produced much more IFN-γ than the CD4−8+ or the CD4+8− DC under all conditions tested.

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