Differential Ability of Occupational Chemical Contact and Respiratory Allergens to Cause Immediate and Delayed Dermal Hypersensitivity Reactions in Mice

Abstract

Trimellitic anhydride (TMA) is known to cause occupational respiratory allergy associated with the presence of specific IgE antibody. Other chemicals, such as 2,4-dinitrochlorobenzene (DNCB), while exhibiting a clear potential for contact sensitization, apparently lack the ability to induce respiratory allergy in man. It has been shown previously that although both chemicals are immunogenic in mice, each provoking contact sensitization, exposure only to TMA results in an IgE antibody response. In the present study, to examine further the characteristics of human allergens, we have compared the ability of TMA and DNCB to elicit immediate and delayed cutaneous hypersensitivity reactions in mice. Topical exposure to both chemicals resulted in delayed (24 h) hypersensitivity. However, only TMA induced, in addition, an immediate (1 h) dermal reaction following local challenge. Serum from TMA-immune mice, but not from untreated mice or mice sensitized with DNCB, was able to transfer immediate hypersensitivity to naive recipients. The kinetics of passive sensitization with TMA-immune serum, together with the fact that immediate hypersensitivity to DNCB could be induced with monoclonal IgE anti-dinitrophenol (DNP) antibody, suggests that the immediate dermal responses caused by TMA are effected by hapten-specific IgE. These data demonstrate that different classes of occupational chemical allergen exhibit a variable potential to elicit immediate and delayed dermal hypersensitivity reactions in mice, and provide a novel approach to the classification and characterization of human allergens.

Impact of Cutaneous IL-10 on Resident Epidermal Langerhans’ Cells and the Development of Polarized Immune Responses

“…These data suggest that one function of IL-10 in the skin is to down-regulate cutaneous inflammatory responses via inhibition of proinflammatory cytokines such as IL-1␤, an activity of this cytokine that has been demonstrated previously in the skin (18,27). Despite the lack of early IL-1␤ expression in the immune response to TMA, this allergen is able to stimulate LC migration, DC accumulation, and lymph node activation, albeit with delayed kinetics compared with DNCB, and to stimulate IgE Ab production, Th2 cytokine expression, and challenge-induced cell-mediated cutaneous inflammatory responses (12,28,29). However, analogous with responses stimulated by another Th2-inducing chemical allergen, FITC, the skin reactions provoked by challenge of TMA-sensitized mice are likely to be mediated by Th2-type cells rather than by IFN-␥-expressing Th1-type cells, the cellular effectors of classical contact hypersensitivity reactions (30).…”

An Aspirin-Triggered Lipoxin A4 Stable Analog Displays a Unique Topical Anti-Inflammatory Profile

“…Sensitization with the occupational contact allergen trimellitic anhydride (TMA) induces a DTH reaction, with prominent eosinophil infiltration 24 h after challenge (24), which, in contrast to other types of acute contact dermatitis, is characterized by a mixed Th1/Th2 reaction. Mice were sensitized on days 0 and 1 by a single application of 50 l of 3% (w/v) TMA in acetone/isopropylmyristate (80/20) onto a shaven area of 2 ϫ 2 cm on the right flank.…”

Contribution of CD4+ and CD8+ T lymphocyte subsets to the cytokine secretion patterns induced in mice during sensitization to contact and respiratory chemical allergens

“…[7][8][9][10] We have shown previously that chemical allergens of different types induce divergent immune responses characteristic of selective Th cell subset activation in BALB/c strain mice. [11][12][13][14] Such responses to contact and respiratory chemical allergens are associated, respectively, with the emergence of Th1-and Th2-type cytokine production patterns. [15][16][17] Thus, draining lymph node cells (LNC) isolated from mice treated repeatedly on the skin with contact sensitizing chemicals express high levels of IFN-g, but only low or undetectable levels of IL-4 and IL-10.…”