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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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 3

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Airway inflammatory responses and serum antibody production in i.n. OVA–...
Airway inflammatory responses and serum antibody production in i.n. OVA–sensitized IL-4–/–mice. C57BL/6 (WT) or IL-4–/– mice were initially exposed to i.n. OVA (100 μg) on days 0–2, and then challenged with i.n. OVA (25 μg) on days 14, 15, 18, and 19. (a) On day 21, mice were sacrificed, BAL was performed, and total cell yield and differential counts in cytospin preparations from individual mice were determined. Data were pooled from 2 experiments and are reported as mean ± SEM of 8 (WT) or 9 (IL-4–/–) mice per group. Both the total number of cells recovered by BAL and the number of each cell type are shown. Statistical significance between WT and IL-4–/– groups was determined by unpaired Student’s t test. (b) Serum was obtained for measurement of antibodies by ELISA on day 21. Data points represent values for individual mice with the mean indicated, and are from 1 representative experiment of 2 with similar results.