Document Detail


Optimization of methods to study pulmonary dendritic cell migration reveals distinct capacities of DC subsets to acquire soluble versus particulate antigen.
MedLine Citation:
PMID:  18662693     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Dendritic cell migration from the airway to lymph nodes is a key event in the development of airway immunity during infection, allergy, and vaccination. To identify the best approaches to investigate DC migration to lung-draining lymph nodes, we directly compared three methods previously used to track DC migration: airway administration of fluorescent OVA, latex beads, or carboxyfluorescein succinimidyl ester (CFSE). We show that two of the methods employed in optimal conditions-administration of fluorescent OVA or latex particles-have broadly relevant utility in studies of pulmonary DC migration, both in the presence and absence of inflammatory mediators. However, CFSE was of limited value because it induced a robust airway inflammatory response upon instillation. Unexpectedly, antigen-loaded tracers with distinct physical properties differently affected the populations that acquired the tracers and the overall T cell response. Specifically, soluble OVA and OVA formulated as a particulate after conjugation to latex beads were acquired in different proportions in vivo by the two characterized subsets of pulmonary DCs: CD11b(hi)CD103(-) and CD11b(lo)CD103(+)langerin(+) DC populations. Consequently, and in line with recent studies that these two subsets of DCs respectively activate CD4(+) and CD8(+) lymphocyte populations, the physical nature of the antigen delivery vehicle strongly influenced the degree of CD4(+) versus CD8(+) OVA-specific T cell activation. This finding suggests that changes in the physical presentation of the same antigen delivered to the airway during natural immune responses or vaccinations may markedly affect the character of the T cell response that ensues.
Authors:
Claudia Jakubzick; Julie Helft; Theodore J Kaplan; Gwendalyn J Randolph
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-07-26
Journal Detail:
Title:  Journal of immunological methods     Volume:  337     ISSN:  0022-1759     ISO Abbreviation:  J. Immunol. Methods     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-25     Completed Date:  2008-10-07     Revised Date:  2010-12-30    
Medline Journal Info:
Nlm Unique ID:  1305440     Medline TA:  J Immunol Methods     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  121-31     Citation Subset:  IM    
Affiliation:
Department of Gene and Cell Medicine, Icahn Research Institute, Mount Sinai School of Medicine, NY, New York 10029, United States. claudia.jakubzick@mssm.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigen Presentation*
Antigens, CD / analysis
Antigens, CD11b / analysis
CD8-Positive T-Lymphocytes / immunology
Cell Movement
Dendritic Cells / physiology*
Integrin alpha Chains / analysis
Lung / immunology*
Lymph Nodes / immunology
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Pertussis Toxin / pharmacology
Grant Support
ID/Acronym/Agency:
AI49653/AI/NIAID NIH HHS; R01 AI061741-02/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, CD11b; 0/Integrin alpha Chains; 0/alpha E integrins; EC 2.4.2.31/Pertussis Toxin

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