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ABSTRACT: Respiratory and contact chemical allergens provoke differential immune responses in mice, stimulating preferentially T helper-2 (TH2) and TH1 cells, respectively. In an attempt to discover whether such differences are effected at the level of antigen handling and presentation we have examined the effect of topical exposure to trimellitic anhydride (TMA), a respiratory allergen, and 2,4-dinitrochlorobenzene (DNCB), a contact allergen, on Langerhans cell (LC) MHC class II (Ia) expression. Neither chemical caused a significant change in LC size. As measured by analytical flow cytometry, exposure to DNCB resulted in a time-dependent increase in LC Ia expression that exceeded 160% of control values within 24 h. Exposure to concentrations of TMA that caused an equivalent activation of draining lymph nodes failed to affect Ia expression by LC. Application of sodium lauryl sulfate at concentrations that caused edema also failed to influence LC Ia. These data demonstrate that TMA and DNCB exert differential effects on epidermal LC, possibly indicative of differences in antigen handling.
Journal of Investigative Dermatology 12/1992; 99(5):107S-108S. · 6.31 Impact Factor
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ABSTRACT: Following skin sensitization of mice, epidermal Langerhans cells (LC) are stimulated to migrate via the afferent lymphatics to the draining lymph nodes. Previous studies have demonstrated that, while in transit, LC acquire the characteristics of mature dendritic cells (DC) and develop into potent immunostimulatory cells. In the present study the expression by LC and lymph node DC of intercellular adhesion molecule-1 (ICAM-1) has been compared. Freshly-isolated LC expressed only very low levels of ICAM-1. In contrast lymph node DC, irrespective of whether they were isolated from resting lymph nodes or from activated lymph nodes draining the site of sensitization with oxazolone, exhibited significant membrane ICAM-1. As a substantial proportion of the DC found within the draining nodes of skin sensitized mice derive from epidermal LC it is apparent that, during migration from the skin, LC are induced to express increased ICAM-1. Such is compatible with the development of LC into effective antigen presenting cells.
Immunology Letters 05/1992; 32(2):105-10. · 2.53 Impact Factor
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ABSTRACT: Chemical allergens differ with respect to the type of hypersensitivity reactions they preferentially elicit. Some chemicals, such as trimellitic anhydride (TMA), have the potential to induce both contact and respiratory hypersensitivity. Other chemicals cause only contact allergy. For example, 2,4-dinitrochlorobenzene (DNCB), a potent contact allergen, appears not to induce respiratory sensitization. In previous studies we have shown that topical exposure of mice to TMA and DNCB, under conditions of equivalent immunogenicity with respect to draining lymph node activation and contact sensitization, caused qualitatively different antibody responses. While the chemicals provoked IgG anti-hapten antibody responses of equivalent magnitude, only TMA induced an IgE response, and DNCB caused a significantly stronger IgG2a response. These data are consistent with the preferential activation by DNCB and TMA of Th1 and Th2 cells respectively. The purpose of the present study was to examine whether the qualitative differences in immune responses stimulated by these chemicals is reflected by variable affects on Langerhans cells (LC) in situ. Mice were exposed to concentrations of DNCB (1%) and TMA (50%) which caused equivalent levels of contact sensitization. Under these conditions topical exposure to DNCB, but not to TMA, or to vehicle alone, resulted in increased expression by LC of Ia antigen. Similar treatment with an irritant concentration (20%) of sodium dodecyl sulphate failed to influence Ia expression by LC. These data indicate that, at concentrations which induce similar levels of skin sensitization, not all contact allergens cause rapid changes in LC Ia expression, and that the qualitative differences in immune responses elicited by chemical allergens DNCB and TMA is associated with variable effects on LC.
Journal of clinical & laboratory immunology 02/1992; 37(2):65-81.
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ABSTRACT: Following exposure of mice to contact sensitizing chemicals, dendritic cells (DC) rapidly accumulate in the draining lymph nodes. A proportion, at least, of the DC which arrive in the nodes bear significant amounts of antigen and are derived from epidermal Langerhans' cells (LC). It is of interest that although LC are relatively inefficient antigen-presenting cells, the antigen-bearing DC found within draining nodes are potent accessory cells and induce immune responses both in vitro and in vivo. Previous in vitro studies have shown that during culture in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF), LC are subject to a functional and phenotypic maturation characterized by the development of effective accessory cell function and elevated membrane Ia antigen expression. We have hypothesized previously that LC may undergo a similar maturation in vivo as they move to the draining lymph nodes following receipt of the stimulus to migrate. As maturation in vitro is accompanied by increased Ia, we have examined the expression of this molecule on epidermal LC and lymph node DC during the induction phase of contact sensitization. The data reported provide evidence that peripheral lymph node DC, irrespective of whether they are derived from draining or resting nodes, and irrespective of whether or not they bear antigen, express comparable high levels of Ia antigen. In contrast, compared with DC, freshly isolated LC have considerably less (on average five times less) Ia antigen. These results indicate that during migration from the skin to lymphoid tissue LC are subject to a phenotypic maturation, comparable with that observed in vitro, and consistent with the acquisition of active antigen-presenting cell function.
Immunology 12/1991; 74(3):414-9. · 3.32 Impact Factor
