Document Detail


Conditioning of the injection site with CpG enhances the migration of adoptively transferred dendritic cells and endogenous CD8+ T-cell responses.
MedLine Citation:
PMID:  20145551     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The efficiency of immunotherapy using tumor-antigen-loaded dendritic cells (DCs) is severely limited by the impaired migration of injected cells from the application site to the draining lymph nodes. As described earlier, pretreatment of the injection site with inflammatory cytokines enhances DC migration. We wanted to test whether toll-like receptor (TLR) ligands can improve migration of murine bone marrow-derived DC (BMDC) and the subsequent T-cell responses. For this purpose, we established an experimental setup closely resembling human vaccination protocols that served to investigate DC migration from the skin to the draining lymph nodes. We observed that BMDC, matured with a cytokine cocktail (tumor necrosis factor-alpha, interleukin-beta, interleukin-6, prostaglandin E2), strongly expressed CCR7. The migration efficiency of adoptively transferred mature BMDCs was determined by the number of cells injected and the application site. We decided to inject DC intradermally into the ear skin and investigated the effects of pretreatment of the injection site with various TLR ligands. Conditioning of the skin site with the TLR ligands CpG and Peptidoglycan increased the number of DCs arriving in the lymph node. Mechanical stress applied to the skin, such as tape stripping of the skin was equally effective. Importantly, only pretreatment with CpG enhanced responses of endogenous CD8 T cells. Thus, conditioning of the injection site with the TLR ligand CpG could be a new promising way to improve the outcome of DC immunotherapy.
Authors:
Christoph H Tripp; Susanne Ebner; Gudrun Ratzinger; Nikolaus Romani; Patrizia Stoitzner
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunotherapy (Hagerstown, Md. : 1997)     Volume:  33     ISSN:  1537-4513     ISO Abbreviation:  J. Immunother.     Publication Date:    2010 Feb-Mar
Date Detail:
Created Date:  2010-02-24     Completed Date:  2010-06-14     Revised Date:  2014-02-05    
Medline Journal Info:
Nlm Unique ID:  9706083     Medline TA:  J Immunother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  115-25     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adoptive Transfer*
Animals
Antigens, Neoplasm / immunology,  metabolism*
Cancer Vaccines*
Cell Movement / drug effects*,  immunology
Cells, Cultured
DNA / pharmacology
Dendritic Cells / drug effects,  immunology,  metabolism*,  pathology
Imidazoles / pharmacology
Injections, Intradermal
Lipopolysaccharides / pharmacology
Lymph Nodes / drug effects,  pathology
Mice
Mice, Inbred C57BL
Oligodeoxyribonucleotides
Peptidoglycan / pharmacology
Receptors, CCR7 / immunology,  metabolism
Skin / drug effects,  pathology
Toll-Like Receptors / agonists
Grant Support
ID/Acronym/Agency:
L 120-B13//Austrian Science Fund FWF
Chemical
Reg. No./Substance:
0/Antigens, Neoplasm; 0/Cancer Vaccines; 0/Ccr7 protein, mouse; 0/CpG ODN 1826; 0/Imidazoles; 0/Lipopolysaccharides; 0/Oligodeoxyribonucleotides; 0/Peptidoglycan; 0/Receptors, CCR7; 0/Toll-Like Receptors; 9007-49-2/DNA; V3DMU7PVXF/resiquimod

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