Document Detail


CD80 and CD86 differentially regulate mechanical interactions of T-cells with antigen-presenting dendritic cells and B-cells.
MedLine Citation:
PMID:  23024807     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Functional T-cell responses are initiated by physical interactions between T-cells and antigen-presenting cells (APCs), including dendritic cells (DCs) and B-cells. T-cells are activated more effectively by DCs than by B-cells, but little is known about the key molecular mechanisms that underpin the particular potency of DC in triggering T-cell responses. To better understand the influence of physical intercellular interactions on APC efficacy in activating T-cells, we used single cell force spectroscopy to characterize and compare the mechanical forces of interactions between DC:T-cells and B:T-cells. Following antigen stimulation, intercellular interactions of DC:T-cell conjugates were stronger than B:T-cell interactions. DCs induced higher levels of T-cell calcium mobilization and production of IL-2 and IFNγ than were elicited by B-cells, thus suggesting that tight intercellular contacts are important in providing mechanically stable environment to initiate T-cell activation. Blocking antibodies targeting surface co-stimulatory molecules CD80 or CD86 weakened intercellular interactions and dampen T-cell activation, highlighting the amplificatory roles of CD80/86 in regulating APC:T-cell interactions and T-cell functional activation. The variable strength of mechanical forces between DC:T-cells and B:T-cell interactions were not solely dependent on differential APC expression of CD80/86, since DCs were superior to B-cells in promoting strong interactions with T-cells even when CD80 and CD86 were inhibited. These data provide mechanical insights into the effects of co-stimulatory molecules in regulating APC:T-cell interactions.
Authors:
Tong Seng Lim; James Kang Hao Goh; Alessandra Mortellaro; Chwee Teck Lim; Günter J Hämmerling; Paola Ricciardi-Castagnoli
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-09-14
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-10-01     Completed Date:  2013-02-15     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e45185     Citation Subset:  IM    
Affiliation:
Singapore Immunology Network, Agency for Science, Technology and Research (ASTAR), Singapore, Singapore. lim_tong_seng@immunol.a-star.edu.sg
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigen Presentation / immunology
Antigens, CD80 / metabolism*
Antigens, CD86 / metabolism*
B-Lymphocytes / immunology,  metabolism*
Calcium / metabolism
Cell Communication* / immunology
Cell Lineage
Dendritic Cells / immunology,  metabolism*
Histocompatibility Antigens Class I / metabolism
Immunophenotyping
Lymphocyte Activation / immunology
Mice
Mice, Knockout
T-Lymphocytes / immunology,  metabolism*
Chemical
Reg. No./Substance:
0/Antigens, CD80; 0/Antigens, CD86; 0/Histocompatibility Antigens Class I; 7440-70-2/Calcium
Comments/Corrections

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