Source:http://linkedlifedata.com/resource/pubmed/id/18483280
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
2008-5-16
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pubmed:abstractText |
Targeting dendritic cells in vivo by transcutaneous peptide immunization (TCI) represents an efficient immunization strategy to induce tumor-specific CTL because it reflects the physiologic conditions occurring during pathogen infection. Here we show that including a Th1 peptide in TCI can activate preexisting memory Th1 (mTh1) responses and thereby enhance the CTL response. For this purpose, peptide-25, a major Th1 epitope of Ag85B from Mycobacterium tuberculosis, was selected. We adoptively transferred peptide-25-specific mTh1 cells and hgp100-specific naive CTL (pmel-1 TCR transgenic) into C57BL/6 mice. Subsequently, mice were transcutaneously immunized with CTL peptide (hgp100) and Th1 peptide (peptide-25). Five days after TCI, the frequency and function of pmel-1 cells was monitored by intracellular IFN-gamma staining, ELISPOT, and in vivo cytotoxicity assays. TCI efficiently expanded hgp100-specific, IFN-gamma-producing, strongly cytotoxic CD8(+) T cells. Concurrent activation of mTh1 cells by peptide-25 induced a 1.5-fold increase in the number of hgp100-specific CTL with enhanced effector functions. Furthermore, TCI elicited not only prophylactic but also therapeutic antitumor responses that were augmented by peptide-25. These results show that TCI facilitates peptide-specific activation of CD4(+) T cells, responsible for the augmenting effect of peptide-25 on the hgp100-specific CTL response. Because a significant proportion of the Japanese population has been vaccinated with Bacillus Calmette-Guerin, they are likely to possess Ag85B- or peptide-25-specific mTh1 cells. Therefore, concomitant activation of Ag85B- or peptide-25-specific mTh1 cells together with tumor-specific CTL by TCI might augment antitumor immune responses in a sizeable fraction of patients.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1538-7445
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
68
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3941-9
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:18483280-Adoptive Transfer,
pubmed-meshheading:18483280-Animals,
pubmed-meshheading:18483280-Cell Line, Tumor,
pubmed-meshheading:18483280-Epitopes,
pubmed-meshheading:18483280-Immunologic Memory,
pubmed-meshheading:18483280-Interferon-gamma,
pubmed-meshheading:18483280-Leukocytes, Mononuclear,
pubmed-meshheading:18483280-Melanoma, Experimental,
pubmed-meshheading:18483280-Mice,
pubmed-meshheading:18483280-Mice, Inbred C57BL,
pubmed-meshheading:18483280-Mice, Transgenic,
pubmed-meshheading:18483280-Peptides,
pubmed-meshheading:18483280-Skin Neoplasms,
pubmed-meshheading:18483280-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:18483280-Th1 Cells
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pubmed:year |
2008
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pubmed:articleTitle |
Memory Th1 cells augment tumor-specific CTL following transcutaneous peptide immunization.
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pubmed:affiliation |
Department of Immunotherapeutics (Medinet), Graduate School of Medicine, The University of Tokyo, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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