Th2 responses induced by epicutaneous or inhalational protein exposure are differentially dependent on IL-4
Christina A. Herrick, … , Robert E. Tigelaar, Kim Bottomly
Christina A. Herrick, … , Robert E. Tigelaar, Kim Bottomly
Published March 15, 2000
Citation Information: J Clin Invest. 2000;105(6):765-775. https://doi.org/10.1172/JCI8624.
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Article

Th2 responses induced by epicutaneous or inhalational protein exposure are differentially dependent on IL-4

Abstract

Atopic individuals are predisposed to mounting vigorous Th2-type immune responses to environmental allergens. To determine the factors responsible, animal models that closely mimic natural modes of allergen exposure should prove most informative. Therefore, we investigated the role of IL-4, a known Th2-promoting cytokine, in generation of Th2 responses after exposure of either the skin or airway to soluble protein. Compared with wild-type (WT) mice, IL-4–deficient (IL-4–/–) mice showed markedly impaired Th2 activation after primary exposure to inhaled ovalbumin (OVA), with decreased OVA-specific IgG1 and IgE, and significantly fewer eosinophils in bronchoalveolar lavage (BAL) fluid after airway challenge. In contrast, IL-4–/– mice initially exposed to epicutaneous (e.c.) OVA mounted Th2 responses equivalent to responses in WT mice, with high numbers of eosinophils in BAL fluid. Because Th2 responses were not induced by e.c. OVA exposure in Stat6–/– mice (mice lacking signal transducer and activator of transcription 6), the role of IL-13 was tested. In vivo depletion of IL-13 prevented Th2 responses induced by e.c. OVA exposure in IL-4–/– mice. These data demonstrate a marked difference in the IL-4 dependence of Th2 responses generated at two anatomic sites of natural allergen encounter and identify the skin as a particularly potent site for Th2 sensitization.

Authors

Christina A. Herrick, Heather MacLeod, Earl Glusac, Robert E. Tigelaar, Kim Bottomly

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Figure 6

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Comparison of lung inflammatory responses after airway challenge of epic...
Comparison of lung inflammatory responses after airway challenge of epicutaneously sensitized WT or IL-4–/– mice. C57BL/6 WT or IL-4–/– mice were initially exposed to e.c. OVA (100 μg) on day 0, challenged with i.n. OVA (25 μg) on days 14, 15, 18, and 19, and sacrificed on day 21. (a) In some experiments, lungs were harvested, processed for routine histologic analysis (H&E staining), and scored for inflammation (see Methods). Data are from 3 experiments and are reported as the mean ± SEM of 11 (WT) or 13 (IL-4–/–) mice per group. (b and c) In other experiments, lungs were harvested from 5–10 mice per group and pooled. Inflammatory cells were isolated by enzymatic digestion. Cells were then either analyzed by flow cytometry or restimulated in vitro by culture with OVA (100 μg/mL) for 48 hours, and cytokine levels were measured in supernatants by ELISA. Data are reported as the number of cells isolated per mouse from a representative experiment (b), or as the mean ± SEM cytokine concentration in culture supernatants from 2 experiments (c).