期刊
JOURNAL OF IMMUNOLOGY
卷 182, 期 7, 页码 4200-4207出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0802286
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资金
- Deutsche Forschungsgemeinschaft
- National Health and Medical Research Council of Australia (NHMRC)
- Howard Hughes Medical Institute
- NHMRC Independent Research Institute Infrastructure Support Scheme [361646]
- Victorian State Government Operational Infrastructure
- Leukemia and Lymphoma Society
- Fondation pour la Recherche Medicale
Mouse spleens contain three major dendritic cell (DC) populations: plasmacytoid DC, conventional CD8(+)CD24(+) DC (CD8(+) DC), and conventional CD8(-)CD24(-) DC (CD8(-) DC). We have previously shown that CD8(+) DC are the major cross-presenting subtype in vivo and are the main inducers of antiviral cytotoxic T lymphocyte responses. Here we show that after depletion of CD8(+) DC, the only DC capable of viral Ag presentation was a small subset that expresses CD24 but not CD8. This CD8(-)CD24(+) DC population is greatly expanded in mice treated with the DC growth factor FMS-like tyrosine kinase 3 ligand. The CD8(-)CD24(+) DC represent an immediate precursor of CD8(+) DC, as demonstrated by their expression pattern of characteristic markers of CD8(+) DC, their capacity to cross-present in vitro, and their conversion into CD8(+) DC upon adoptive transfer into recipient mice. Accordingly, the lifespan of transferred CD8(-)CD24(+) DC in vivo was greatly enhanced as compared with terminally differentiated CD8(+) DC. Moreover, in a vaccination protocol, CD8(-)CD24(+) DC induced stronger T cell responses and accelerated viral clearance of HSV-1 compared with CD8(+) DC. Our results demonstrate that the ability to cross-present first appears in an immediate precursor population of CD8(+) DC that does not yet express CD8. The enhanced capacity of CD8(-)CD24(+) DC to induce immune responses upon adoptive transfer makes them an attractive novel tool for DC-based immunotherapies. The Journal of Immunology, 2009, 182: 4200-4207.
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