Linked Life Data

18804283

Source:http://linkedlifedata.com/resource/pubmed/id/18804283

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-10-17
pubmed:abstractText
Heat shock proteins (HSPs) induce cross-presentation of antigens by dendritic cells (DC) as well as DC maturation. These properties make HSP antigen complexes good candidates to prime CD8 T cell responses against tumor-associated antigens. In this study, we analyzed four different members of the HSP70 family fused to a fragment of ovalbumin (OVA) as a model tumor antigen. E. coli-derived recombinant HSP70-OVA fusion proteins efficiently primed antigen-specific cytotoxic T cells in short-term in vivo immunization assays. Because of concerns that the adjuvant effect of HSPs may be due to endotoxin contamination, we studied this issue in detail. Induction of OVA-specific cytotoxicity was significantly decreased in mice deficient for the LPS receptor, TLR4. After careful removal of endotoxins, immunization with HSP70-OVA failed to prime cytotoxic T cell responses. However, we obtained strong in vivo kill responses when endotoxin-depleted HSP70-OVA was used in combination with the TLR9 ligand CpG oligodeoxynucleotide 1668. Importantly, prophylactic and therapeutic treatment with endotoxin-depleted HSP70-OVA together with CpG significantly delayed the outgrowth of OVA-expressing B16 melanoma cells. However, we were unable to detect significant differences in the magnitudes of immune responses against endotoxin-depleted recombinant OVA vs. endotoxin-depleted HSP70-OVA fusion protein. Thus, immunization with recombinant HSP70-antigen fusion protein does not provide an advantage over recombinant antigen alone when combined with a suitable adjuvant. Altogether, our data suggest that the adjuvant effect of the HSP70 part of the fusion protein is completely lost after endotoxin removal.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0161-5890
pubmed:author
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
181-91
pubmed:meshHeading
pubmed-meshheading:18804283-Adjuvants, Immunologic, pubmed-meshheading:18804283-Animals, pubmed-meshheading:18804283-Antigens, pubmed-meshheading:18804283-CD8-Positive T-Lymphocytes, pubmed-meshheading:18804283-Cross-Priming, pubmed-meshheading:18804283-Cytotoxicity, Immunologic, pubmed-meshheading:18804283-Dendritic Cells, pubmed-meshheading:18804283-Endotoxins, pubmed-meshheading:18804283-HSP70 Heat-Shock Proteins, pubmed-meshheading:18804283-Lymphocyte Activation, pubmed-meshheading:18804283-Mice, pubmed-meshheading:18804283-Mice, Inbred C57BL, pubmed-meshheading:18804283-Mice, Transgenic, pubmed-meshheading:18804283-Neoplasms, pubmed-meshheading:18804283-Oligodeoxyribonucleotides, pubmed-meshheading:18804283-Ovalbumin, pubmed-meshheading:18804283-Receptors, Antigen, T-Cell, pubmed-meshheading:18804283-Recombinant Fusion Proteins, pubmed-meshheading:18804283-T-Lymphocytes, Cytotoxic
pubmed:year
2008
pubmed:articleTitle
Heat shock protein-antigen fusions lose their enhanced immunostimulatory capacity after endotoxin depletion.
pubmed:affiliation
Division of Molecular Immunology (D050), German Cancer Research Center (DKFZ), Heidelberg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't