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Antigenic competition in contact sensitivity. Evidence for changes in dendritic cell migration and antigen handling
I Kimber1, S Hill, J A Mitchell
1ICI Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, U.K.
Insights
Antigenic competition in contact sensitivity involves changes in dendritic cells (DC). Pre-exposure to one antigen reduces the response to a second, altering DC frequency and antigen presentation in lymph nodes.
Area of Science:
- Immunology
- Cell Biology
Background:
- Contact sensitivity is an immune response mediated by T cells.
- Antigenic competition describes the phenomenon where exposure to one antigen can suppress the immune response to a subsequent, different antigen.
- Dendritic cells (DC) are crucial antigen-presenting cells that initiate adaptive immune responses.
Purpose of the Study:
- To investigate the role and characteristics of dendritic cells (DC) in the context of antigenic competition within the draining lymph nodes during contact sensitivity.
- To determine how prior exposure to one sensitizing agent affects the DC response to a subsequent antigen.
Main Methods:
- Mice were sensitized with oxazolone, followed by challenge with fluorescein isothiocyanate (FITC).
- Draining lymph nodes were analyzed for the frequency and antigen-bearing characteristics of dendritic cells (DC).
- Flow cytometry was used to quantify antigen presentation on DC.
Main Results:
- Pre-exposure to oxazolone significantly depressed subsequent FITC-induced lymph node cell (LNC) proliferation.
- Antigenic competition was associated with an increased frequency of DC in draining lymph nodes.
- However, the percentage of antigen-bearing DC and the median amount of antigen per DC were reduced.
Conclusions:
- Induced changes in dendritic cell (DC) behavior, including altered migration and antigen presentation, are associated with the reduced immune response observed during antigenic competition in contact sensitivity.
- Systemic effects on DC migration following initial antigen exposure may contribute to the observed changes in DC characteristics during competition.
Abstract:
The frequency and antigen-bearing characteristics of dendritic cells (DC) within draining lymph nodes have been examined during antigenic competition in contact sensitivity. Pre-exposure of mice to oxazolone on the flank resulted in a marked depression of subsequent fluorescein isothiocyanate (FITC)-induced lymph node cell (LNC) proliferation. Antigenic competition was associated with an increased frequency of DC in the draining lymph nodes, but also with a reduced amount of antigen per cell. Thus, at 24 hr the draining nodes of FITC-challenged mice previously exposed to oxazolone exhibited an increased number of DC compared with control animals. Flow cytometric analysis revealed, however, that the percentage of antigen-bearing DC was reduced and that the median amount of antigen borne by DC was lower. Since exposure to oxazolone caused a significant increase in the frequency of DC in distant nodes, the changes observed in antigenic competition may, at least in part, be attributable to systemic effects on DC migration following application of the first antigen. These data indicate that the reduced primary proliferative response which characterizes antigenic competition in contact sensitivity is associated with, and may result from, induced changes in dendritic cell behaviour.
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