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J Clin Invest. 1998 April 15; 101(8): 1614–1622.
PMCID: PMC508742

Epicutaneous sensitization with protein antigen induces localized allergic dermatitis and hyperresponsiveness to methacholine after single exposure to aerosolized antigen in mice.


Our understanding of the pathogenesis of atopic dermatitis (AD) and its relationship to asthma remains incomplete. Herein, we describe a murine model of epicutaneous (EC) sensitization to the protein allergen, chicken egg albumin, ovalbumin (OVA), which results in a rise in total and OVA-specific serum IgE and leads to the development of a dermatitis characterized by infiltration of CD3(+) T cells, eosinophils, and neutrophils and by local expression of mRNA for the cytokines IL-4, IL-5, and interferon-gamma. A single exposure of the EC sensitized mice to aerosolized OVA induced eosinophilia in the bronchoalveolar lavage fluid and airway hyperresponsiveness to intravenous methacholine as assessed by measurement of pulmonary dynamic compliance (Cdyn). These results suggest a possible role for EC exposure to antigen in atopic dermatitis and in the development of allergic asthma.

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Selected References

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  • Leung DY. Atopic dermatitis: the skin as a window into the pathogenesis of chronic allergic diseases. J Allergy Clin Immunol. 1995 Sep;96(3):302–319. [PubMed]
  • Leung DY. Immunopathology of atopic dermatitis. Springer Semin Immunopathol. 1992;13(3-4):427–440. [PubMed]
  • Thepen T, Langeveld-Wildschut EG, Bihari IC, van Wichen DF, van Reijsen FC, Mudde GC, Bruijnzeel-Koomen CA. Biphasic response against aeroallergen in atopic dermatitis showing a switch from an initial TH2 response to a TH1 response in situ: an immunocytochemical study. J Allergy Clin Immunol. 1996 Mar;97(3):828–837. [PubMed]
  • Jung K, Linse F, Heller R, Moths C, Goebel R, Neumann C. Adhesion molecules in atopic dermatitis: VCAM-1 and ICAM-1 expression is increased in healthy-appearing skin. Allergy. 1996 Jul;51(7):452–460. [PubMed]
  • Wakita H, Sakamoto T, Tokura Y, Takigawa M. E-selectin and vascular cell adhesion molecule-1 as critical adhesion molecules for infiltration of T lymphocytes and eosinophils in atopic dermatitis. J Cutan Pathol. 1994 Feb;21(1):33–39. [PubMed]
  • Leiferman KM. Eosinophils in atopic dermatitis. J Allergy Clin Immunol. 1994 Dec;94(6 Pt 2):1310–1317. [PubMed]
  • Jones SM, Sampson HA. The role of allergens in atopic dermatitis. Clin Rev Allergy. 1993 Winter;11(4):471–490. [PubMed]
  • Tupker RA, De Monchy JG, Coenraads PJ, Homan A, van der Meer JB. Induction of atopic dermatitis by inhalation of house dust mite. J Allergy Clin Immunol. 1996 May;97(5):1064–1070. [PubMed]
  • Mitchell EB, Crow J, Chapman MD, Jouhal SS, Pope FM, Platts-Mills TA. Basophils in allergen-induced patch test sites in atopic dermatitis. Lancet. 1982 Jan 16;1(8264):127–130. [PubMed]
  • Roberts DL. House dust mite avoidance and atopic dermatitis. Br J Dermatol. 1984 Jun;110(6):735–736. [PubMed]
  • Tan BB, Weald D, Strickland I, Friedmann PS. Double-blind controlled trial of effect of housedust-mite allergen avoidance on atopic dermatitis. Lancet. 1996 Jan 6;347(8993):15–18. [PubMed]
  • Sager N, Feldmann A, Schilling G, Kreitsch P, Neumann C. House dust mite-specific T cells in the skin of subjects with atopic dermatitis: frequency and lymphokine profile in the allergen patch test. J Allergy Clin Immunol. 1992 Apr;89(4):801–810. [PubMed]
  • Saloga J, Renz H, Larsen GL, Gelfand EW. Increased airways responsiveness in mice depends on local challenge with antigen. Am J Respir Crit Care Med. 1994 Jan;149(1):65–70. [PubMed]
  • Wang LF, Lin JY, Hsieh KH, Lin RH. Epicutaneous exposure of protein antigen induces a predominant Th2-like response with high IgE production in mice. J Immunol. 1996 Jun 1;156(11):4077–4082. [PubMed]
  • Renz H, Smith HR, Henson JE, Ray BS, Irvin CG, Gelfand EW. Aerosolized antigen exposure without adjuvant causes increased IgE production and increased airway responsiveness in the mouse. J Allergy Clin Immunol. 1992 Jun;89(6):1127–1138. [PubMed]
  • Mombaerts P, Mizoguchi E, Grusby MJ, Glimcher LH, Bhan AK, Tonegawa S. Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice. Cell. 1993 Oct 22;75(2):274–282. [PubMed]
  • Bouaboula M, Legoux P, Pességué B, Delpech B, Dumont X, Piechaczyk M, Casellas P, Shire D. Standardization of mRNA titration using a polymerase chain reaction method involving co-amplification with a multispecific internal control. J Biol Chem. 1992 Oct 25;267(30):21830–21838. [PubMed]
  • Martin TR, Gerard NP, Galli SJ, Drazen JM. Pulmonary responses to bronchoconstrictor agonists in the mouse. J Appl Physiol (1985) 1988 Jun;64(6):2318–2323. [PubMed]
  • Kroeker JP. Wiener analysis of nonlinear systems using Poisson-Charlier crosscorrelation. Biol Cybern. 1977 Oct 14;27(4):221–227. [PubMed]
  • Bousquet J, Chanez P, Lacoste JY, Barnéon G, Ghavanian N, Enander I, Venge P, Ahlstedt S, Simony-Lafontaine J, Godard P, et al. Eosinophilic inflammation in asthma. N Engl J Med. 1990 Oct 11;323(15):1033–1039. [PubMed]
  • Leiferman KM, Ackerman SJ, Sampson HA, Haugen HS, Venencie PY, Gleich GJ. Dermal deposition of eosinophil-granule major basic protein in atopic dermatitis. Comparison with onchocerciasis. N Engl J Med. 1985 Aug 1;313(5):282–285. [PubMed]
  • Vercelli D, Geha RS. Regulation of isotype switching. Curr Opin Immunol. 1992 Dec;4(6):794–797. [PubMed]
  • Sanderson CJ. Interleukin-5, eosinophils, and disease. Blood. 1992 Jun 15;79(12):3101–3109. [PubMed]
  • Hamid Q, Boguniewicz M, Leung DY. Differential in situ cytokine gene expression in acute versus chronic atopic dermatitis. J Clin Invest. 1994 Aug;94(2):870–876. [PMC free article] [PubMed]
  • Werfel T, Morita A, Grewe M, Renz H, Wahn U, Krutmann J, Kapp A. Allergen specificity of skin-infiltrating T cells is not restricted to a type-2 cytokine pattern in chronic skin lesions of atopic dermatitis. J Invest Dermatol. 1996 Dec;107(6):871–876. [PubMed]
  • Coffman RL, von der Weid T. Multiple pathways for the initiation of T helper 2 (Th2) responses. J Exp Med. 1997 Feb 3;185(3):373–375. [PMC free article] [PubMed]
  • Ranger AM, Das MP, Kuchroo VK, Glimcher LH. B7-2 (CD86) is essential for the development of IL-4-producing T cells. Int Immunol. 1996 Oct;8(10):1549–1560. [PubMed]
  • Kawamura T, Furue M. Comparative analysis of B7-1 and B7-2 expression in Langerhans cells: differential regulation by T helper type 1 and T helper type 2 cytokines. Eur J Immunol. 1995 Jul;25(7):1913–1917. [PubMed]
  • Macaulay AE, DeKruyff RH, Goodnow CC, Umetsu DT. Antigen-specific B cells preferentially induce CD4+ T cells to produce IL-4. J Immunol. 1997 May 1;158(9):4171–4179. [PubMed]
  • Denfeld RW, Hollenbaugh D, Fehrenbach A, Weiss JM, von Leoprechting A, Mai B, Voith U, Schöpf E, Aruffo A, Simon JC. CD40 is functionally expressed on human keratinocytes. Eur J Immunol. 1996 Oct;26(10):2329–2334. [PubMed]
  • Zhang X, Brunner T, Carter L, Dutton RW, Rogers P, Bradley L, Sato T, Reed JC, Green D, Swain SL. Unequal death in T helper cell (Th)1 and Th2 effectors: Th1, but not Th2, effectors undergo rapid Fas/FasL-mediated apoptosis. J Exp Med. 1997 May 19;185(10):1837–1849. [PMC free article] [PubMed]
  • Vezzio N, Sarfati M, Yang LP, Demeure CE, Delespesse G. Human Th2-like cell clones induce IL-12 production by dendritic cells and may express several cytokine profiles. Int Immunol. 1996 Dec;8(12):1963–1970. [PubMed]
  • Hsieh CS, Macatonia SE, Tripp CS, Wolf SF, O'Garra A, Murphy KM. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science. 1993 Apr 23;260(5107):547–549. [PubMed]
  • Seder RA, Gazzinelli R, Sher A, Paul WE. Interleukin 12 acts directly on CD4+ T cells to enhance priming for interferon gamma production and diminishes interleukin 4 inhibition of such priming. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10188–10192. [PubMed]
  • Hu-Li J, Huang H, Ryan J, Paul WE. In differentiated CD4+ T cells, interleukin 4 production is cytokine-autonomous, whereas interferon gamma production is cytokine-dependent. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3189–3194. [PubMed]
  • Clark RA, Adinoff AD. Aeroallergen contact can exacerbate atopic dermatitis: patch tests as a diagnostic tool. J Am Acad Dermatol. 1989 Oct;21(4 Pt 2):863–869. [PubMed]
  • Bruynzeel-Koomen CA, Van Wichen DF, Spry CJ, Venge P, Bruynzeel PL. Active participation of eosinophils in patch test reactions to inhalant allergens in patients with atopic dermatitis. Br J Dermatol. 1988 Feb;118(2):229–238. [PubMed]
  • Hsu CH, Chua KY, Huang SK, Chiang IP, Hsieh KH. Glutathione-S-transferase induces murine dermatitis that resembles human atopic dermatitis. Clin Exp Allergy. 1996 Nov;26(11):1329–1337. [PubMed]
  • Matsuda H, Watanabe N, Geba GP, Sperl J, Tsudzuki M, Hiroi J, Matsumoto M, Ushio H, Saito S, Askenase PW, et al. Development of atopic dermatitis-like skin lesion with IgE hyperproduction in NC/Nga mice. Int Immunol. 1997 Mar;9(3):461–466. [PubMed]
  • Salob SP, Laverty A, Atherton DJ. Bronchial hyperresponsiveness in children with atopic dermatitis. Pediatrics. 1993 Jan;91(1):13–16. [PubMed]
  • MacLean JA, Ownbey R, Luster AD. T cell-dependent regulation of eotaxin in antigen-induced pulmonary eosinophila. J Exp Med. 1996 Oct 1;184(4):1461–1469. [PMC free article] [PubMed]
  • Drazen JM, Arm JP, Austen KF. Sorting out the cytokines of asthma. J Exp Med. 1996 Jan 1;183(1):1–5. [PMC free article] [PubMed]
  • Gonzalo JA, Lloyd CM, Kremer L, Finger E, Martinez-A C, Siegelman MH, Cybulsky M, Gutierrez-Ramos JC. Eosinophil recruitment to the lung in a murine model of allergic inflammation. The role of T cells, chemokines, and adhesion receptors. J Clin Invest. 1996 Nov 15;98(10):2332–2345. [PMC free article] [PubMed]
  • Mehlhop PD, van de Rijn M, Goldberg AB, Brewer JP, Kurup VP, Martin TR, Oettgen HC. Allergen-induced bronchial hyperreactivity and eosinophilic inflammation occur in the absence of IgE in a mouse model of asthma. Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1344–1349. [PubMed]
  • Korsgren M, Erjefält JS, Korsgren O, Sundler F, Persson CG. Allergic eosinophil-rich inflammation develops in lungs and airways of B cell-deficient mice. J Exp Med. 1997 Mar 3;185(5):885–892. [PMC free article] [PubMed]
  • Hamelmann E, Vella AT, Oshiba A, Kappler JW, Marrack P, Gelfand EW. Allergic airway sensitization induces T cell activation but not airway hyperresponsiveness in B cell-deficient mice. Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1350–1355. [PubMed]
  • Mitchell EB, Crow J, Rowntree S, Webster AD, Platts-Mills TA. Cutaneous basophil hypersensitivity to inhalant allergens in atopic dermatitis patients: elicitation of delayed responses containing basophils following local transfer of immune serum but not IgE antibody. J Invest Dermatol. 1984 Oct;83(4):290–295. [PubMed]

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