Dendritic cells from control but not atopic donors respond to contact and respiratory sensitizer treatment in vitro with differential cytokine production and altered stimulatory capacity.
BACKGROUND
Chemical haptens induce both contact and allergic respiratory disease with dendritic cells (DCs) controlling and directing immune responses in vivo. Contact and respiratory haptens may promote differential cytokine production yet distinguishing these effects in vitro remains difficult due to human donor variability. Objective We sought to determine the effect of atopic status on the ability of DC to respond to contact and respiratory sensitizer treatment in vitro as DC from atopic donors are believed to promote Th2-type responses.


METHODS
Enriched DC from control or atopic donors were treated for 4 h with levels of the contact sensitizer 2,4-dinitrochlorobenzene (DNCB) or the respiratory sensitizer trimellitic anhydride (TMA) that did not reduce cell viability. A sensitive intracellular detection technique was used to measure cytokine production, while T cell responses were assessed in a mixed leucocyte reaction.


RESULTS
DC from control, non-atopic, donors produced cytokines differentially in response to sensitizer treatment; DNCB treatment significantly increased the production of Th1 cytokines IL-12 and IFN-gamma while TMA induced the production of IL-13. Control donor DC treated with TMA stimulated less in a mixed leucocyte reaction than untreated cells with any response reduced further by blocking IL-13 in culture. However, DC from atopic donors showed no significant alteration in either cytokine production or T cell stimulatory capacity after sensitizer treatment.


CONCLUSIONS
Haptens modulate DC by changing the production of cytokines that may play a role in T cell stimulation and subsequent polarization of the immune response. DC from atopic donors were unresponsive to chemical sensitizer treatment, and may be deficient in inducing divergent T cell responses.
Holden
N J
NJ
Antigen Presentation Research Group, Imperial College London, Northwick Park and St Marks Hospital Campus, Harrow, UK.
Bedford
P A
PA
McCarthy
N E
NE
Marks
N A
NA
Ind
P W
PW
Jowsey
I R
IR
Basketter
D A
DA
Knight
S C
SC
D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004137:Dinitrochlorobenzene / Q000276:immunology; D005260:Female; D006241:Haptens / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology; D007509:Irritants / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010796:Phthalic Anhydrides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D004137:Dinitrochlorobenzene; D006241:Haptens; D018793:Interleukin-13; D007509:Irritants; D010796:Phthalic Anhydrides; D018664:Interleukin-12; C015559:trimellitic anhydride; D007371:Interferon-gamma