Document Detail

Chemokine programming dendritic cell antigen response: part II - programming antigen presentation to T lymphocytes by partially maintaining immature dendritic cell phenotype.
MedLine Citation:
PMID:  23277917     Owner:  NLM     Status:  MEDLINE    
In a companion article to this study,(1) the successful programming of a JAWSII dendritic cell (DC) line's antigen uptake and processing was demonstrated based on pre-treatment of DCs with a specific 'cocktail' of select chemokines. Chemokine pre-treatment modulated cytokine production before and after DC maturation [by lipopolysaccharide (LPS)]. After DC maturation, it induced an antigen uptake and processing capacity at levels 36% and 82% higher than in immature DCs, respectively. Such programming proffers a potential new approach to enhance vaccine efficiency. Unfortunately, simply enhancing antigen uptake does not guarantee the desired activation and proliferation of lymphocytes, e.g. CD4(+) T cells. In this study, phenotype changes and antigen presentation capacity of chemokine pre-treated murine bone marrow-derived DCs were examined in long-term co-culture with antigen-specific CD4(+) T cells to quantify how chemokine pre-treatment may impact the adaptive immune response. When a model antigen, ovalbumin (OVA), was added after intentional LPS maturation of chemokine-treated DCs, OVA-biased CD4(+) T-cell proliferation was initiated from ~ 100% more undivided naive T cells as compared to DCs treated only with LPS. Secretion of the cytokines interferon-γ, interleukin-1β, interleukin-2 and interleukin-10 in the CD4(+) T cell : DC co-culture (with or without chemokine pre-treatment) were essentially the same. Chemokine programming of DCs with a 7 : 3 ratio of CCL3 : CCL19 followed by LPS treatment maintained partial immature phenotypes of DCs, as indicated by surface marker (CD80 and CD86) expression over time. Results here and in our companion paper suggest that chemokine programming of DCs may provide a novel immunotherapy strategy to obviate the natural endocytosis limit of DC antigen uptake, thus potentially increasing DC-based vaccine efficiency.
Jaehyung Park; James D Bryers
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Immunology     Volume:  139     ISSN:  1365-2567     ISO Abbreviation:  Immunology     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-09     Completed Date:  2013-06-07     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  England    
Other Details:
Languages:  eng     Pagination:  88-99     Citation Subset:  IM    
Copyright Information:
© 2012 Blackwell Publishing Ltd.
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MeSH Terms
Antigen Presentation / drug effects,  physiology*
Antigens, CD80 / immunology,  metabolism
Antigens, CD86 / immunology,  metabolism
CD4-Positive T-Lymphocytes / cytology,  immunology*,  metabolism
Cells, Cultured
Chemokine CCL19 / immunology*,  pharmacology
Chemokine CCL3 / immunology*,  pharmacology
Cytokines / immunology,  secretion
Dendritic Cells / cytology,  immunology*,  metabolism
Endocytosis / drug effects,  physiology*
Vaccines / immunology
Grant Support
Reg. No./Substance:
0/Antigens, CD80; 0/Antigens, CD86; 0/Ccl19 protein, mouse; 0/Ccl3 protein, mouse; 0/Cd86 protein, mouse; 0/Chemokine CCL19; 0/Chemokine CCL3; 0/Cytokines; 0/Vaccines

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