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rdf:type |
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lifeskim:mentions |
umls-concept:C0010749,
umls-concept:C0011306,
umls-concept:C0019409,
umls-concept:C0038661,
umls-concept:C0085358,
umls-concept:C0205245,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1515021,
umls-concept:C1533685,
umls-concept:C1706438,
umls-concept:C2698600
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pubmed:issue |
8
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pubmed:dateCreated |
2008-2-28
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pubmed:abstractText |
Cross-presentation as a fundamental pathway of activating CD8(+) T cells has been well established. So far the application of this concept in vivo is limited, and the mechanisms that specialize CD8(+) dendritic cells (DCs) for this task are not fully understood. Here we take advantage of the specific cytosolic export feature of cross-presenting DCs together with the property of cytosolic cytochrome c (cyt c) in initiating Apaf-1-dependent apoptosis selectively in cross-presenting DCs. A single i.v. injection of cyt c in B6 mice produced a 2- to 3-fold reduction in splenic CD8(+) DCs but not in Apaf-1-deficient mice. Functional studies both in vivo and in vitro showed that cyt c profoundly abrogated OVA-specific CD8(+) T cell proliferation through its apoptosis-inducing effect on cross-presenting DCs. More importantly, in vivo injection of cyt c abolished the induction of cytotoxic T lymphocytes to exogenous antigen and reduced subsequent immunity to tumor challenge. In addition, only a proportion of CD8(+) DCs that express abundant IL-12 and Toll-like receptor 3 were efficient cross-presenters. Our data support the hypothesis that cross-presentation in vivo requires cytosolic diversion of endocytosed proteins, conferring cross-presentation specialization to a proportion of CD8(+) DCs. We propose that DCs incapable of such transfer, even within the CD8(+) DC subset, are unable to cross-present. Our model opens an avenue to specifically target cross-presenting DCs in vivo for manipulating cytotoxic T lymphocyte responses toward infections, tumors, and transplants.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-10559964,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-10706685,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-10821864,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-11120766,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-11313382,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-12021309,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-12374983,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-12383197,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-12461077,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-12598895,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-1315736,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-14508489,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-14508490,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-14659909,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-14751761,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-14764661,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-15184678,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-15233723,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-15308097,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-15592842,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-15711573,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-15733829,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-15761154,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-15907471,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-16157687,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-16326087,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-16406699,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-16678772,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-16785533,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-16807294,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-16818754,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-16839887,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-17027300,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-2253683,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-3906410,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-7690960,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-8287475,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-9022030,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-9553774,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272486-9927689
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1091-6490
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
26
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pubmed:volume |
105
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3029-34
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:18272486-Animals,
pubmed-meshheading:18272486-Antigens, CD8,
pubmed-meshheading:18272486-Apoptosis,
pubmed-meshheading:18272486-Apoptotic Protease-Activating Factor 1,
pubmed-meshheading:18272486-CD8-Positive T-Lymphocytes,
pubmed-meshheading:18272486-Cross-Priming,
pubmed-meshheading:18272486-Cytochromes c,
pubmed-meshheading:18272486-Dendritic Cells,
pubmed-meshheading:18272486-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:18272486-Flow Cytometry,
pubmed-meshheading:18272486-Fluorescent Antibody Technique,
pubmed-meshheading:18272486-Mice,
pubmed-meshheading:18272486-Mice, Inbred C57BL,
pubmed-meshheading:18272486-Spleen
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pubmed:year |
2008
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pubmed:articleTitle |
Selective suicide of cross-presenting CD8+ dendritic cells by cytochrome c injection shows functional heterogeneity within this subset.
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pubmed:affiliation |
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville VIC 3050, Australia.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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