Inducible interleukin-4-secreting cells provoked in mice during chemical sensitization.
It has been demonstrated previously that chemical contact and respiratory allergens differ with respect to the quality of immune responses they will provoke in mice. Trimellitic anhydride (TMA), a human respiratory allergen, induces in mice responses consistent with the preferential activation of Th2-type cells, resulting in the production of IgE anti-hapten antibody and an increase in the serum concentration of IgE. In contrast, oxazolone (OX), a potent contact allergen considered not to cause respiratory hypersensitivity, induces instead Th1-type responses in mice characterized by vigorous IgG2a antibody production and a failure to elicit IgE. In the present study we have extended these investigations and have examined the capacity of these chemicals to stimulate inducible interleukin-4 (IL-4) production by draining lymph node cells (LNC). IL-4 was measured in the supernatants of draining LNC cultured for various periods in the presence or absence of concanavalin A (Con A). Following primary topical exposure to the chemical allergens, Con A-stimulated LNC from OX-treated mice secreted significantly more IL-4 than did LNC from mice exposed to trimellitic anhydride (TMA). A different pattern of IL-4 secretion was observed following culture with Con A of LNC prepared from lymph nodes draining the sites of secondary exposure to these chemicals. In this case significantly higher concentrations of IL-4 were produced by TMA-treated mice. Detectable levels of IL-4 (> 300 pg/ml) were not found following culture of draining LNC from sensitized mice in the absence of Con A or following culture of LNC from naive mice with or without Con A. These data demonstrate that chemical allergens of different types stimulate discrete and changing patterns of inducible IL-4 synthesis consistent with the selective activation of Th-cell subpopulations.
Zeneca Central Toxicology Laboratory, Macclesfield, U.K.
R J
RJ
Dearman
L S
LS
Ramdin
D A
DA
Basketter
I
I
Kimber
D000485:Allergens / Q000276:immunology*; D000818:Animals; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis*; D007700:Kinetics; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010081:Oxazolone / Q000276:immunology*; D010796:Phthalic Anhydrides / Q000276:immunology*
D000485:Allergens; D010796:Phthalic Anhydrides; D003208:Concanavalin A; D010081:Oxazolone; D015847:Interleukin-4; C015559:trimellitic anhydride