{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T14:00:58Z","timestamp":1791036058429,"version":"4.1.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2004,6,15]],"date-time":"2004-06-15T00:00:00Z","timestamp":1087257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,6,15]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>The pathophysiological and immunological characteristics of allergic immune responses are controlled by a variety of factors. We have studied the extent to which the route of sensitization influences allergen-specific IgE synthesis and local airway inflammation using a mouse model of allergic sensitization to the major birch pollen allergen Bet v 1. Sensitization of BALB\/c mice with recombinant (r)Bet v 1 was performed using intraperitoneal (IP), subcutaneous (SC) or aerosol (AS) sensitization protocols. Mice were analysed for allergen-specific serum antibodies by ELISA and IgE-dependent basophil degranulation. Proliferative responses and cytokine production of splenocytes were measured upon Bet v 1 stimulation in vitro. Bronchoalveolar lavages were performed after airway challenge with aerosolized birch pollen extract for assessment of eosinophilic airway inflammation and local cytokine production in vivo. Highest allergen specific IgE levels and IgE-dependent basophil degranulation were achieved using the SC route. High IL-5 production by spleen and lung cells was associated with pronounced eosinophilia in bronchoalveolar lavages. After IP sensitization, despite giving the highest IgG levels, only low IgE levels, basophil degranulation and IL-5 production were seen. On the other hand, AS sensitization, resulting in the lowest systemic IgE and IL-5 levels, led to a comparably strong airway inflammation as the SC route. Our finding that the route of sensitization can result in a dissociation of local and systemic immune responses may contribute to a better understanding of the pathogenesis of allergic diseases and help to develop new treatment strategies.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2004.02519.x","type":"journal-article","created":{"date-parts":[[2004,6,15]],"date-time":"2004-06-15T19:24:39Z","timestamp":1087327479000},"page":"12-18","source":"Crossref","is-referenced-by-count":40,"title":["Influence of the route of sensitization on local and systemic immune responses in a murine model of type I allergy"],"prefix":"10.1093","volume":"137","author":[{"given":"A","family":"REPA","sequence":"first","affiliation":[{"name":"Department of Pathophysiology"},{"name":"Department of Paediatrics, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"WILD","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"HUFNAGL","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"WINKLER","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"BOHLE","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"POLLAK","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U","family":"WIEDERMANN","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,6,15]]},"reference":[{"key":"2022011223190606200_b1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/978-1-4615-5855-2_46","article-title":"In situ detection of cytokines in allergic inflammation","volume":"409","author":"Hamid","year":"1996","journal-title":"Adv Exp Med Biol"},{"key":"2022011223190606200_b2","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0065-2776(08)60536-2","article-title":"Mechanism and regulation of immunoglobulin isotype switching","volume":"54","author":"Coffman","year":"1993","journal-title":"Adv Immunol"},{"key":"2022011223190606200_b3","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0091-6749(98)70080-6","article-title":"The role of IL-13 and its receptor in allergy and inflammatory responses","volume":"102","author":"De Vries","year":"1998","journal-title":"J Allergy Clin Immunol"},{"key":"2022011223190606200_b4","doi-asserted-by":"crossref","first-page":"3730","DOI":"10.1073\/pnas.90.8.3730","article-title":"Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells","volume":"90","author":"Punnonen","year":"1993","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022011223190606200_b5","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1084\/jem.188.2.399","article-title":"Interleukin (IL)-4-independent induction of immunoglobulin (Ig) E, and perturbation of T cell development in transgenic mice expressing IL-13","volume":"188","author":"Emson","year":"1998","journal-title":"J Exp Med"},{"key":"2022011223190606200_b6","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1378\/chest.103.4.1178","article-title":"Allergen-induced recruitment of inflammatory cells in lavage 3 and 24\u2003h after challenge in allergic asthmatic lungs","volume":"103","author":"Aalbers","year":"1993","journal-title":"Chest"},{"key":"2022011223190606200_b7","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1164\/ajrccm.160.2.9809130","article-title":"Kinetics of allergen-induced airway eosinophilic cytokine production and airway inflammation","volume":"160","author":"Gauvreau","year":"1999","journal-title":"Am J Respir Crit Care Med"},{"key":"2022011223190606200_b8","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1067\/mai.2001.119149","article-title":"The trials and tribulations of IL-5, eosinophils, and allergic asthma","volume":"108","author":"O'Byrne","year":"2001","journal-title":"J Allergy Clin Immunol"},{"key":"2022011223190606200_b9","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S1471-4892(03)00069-9","article-title":"Chemokines in allergic airway disease","volume":"3","author":"Lloyd","year":"2003","journal-title":"Curr Opin Pharmacol"},{"key":"2022011223190606200_b10","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1084\/jem.191.2.265","article-title":"CC chemokine receptor (CCR) 3\/eotaxin is followed by CCR4\/monocyte-derived chemokine in mediating pulmonary T helper lymphocyte type 2 recruitment after serial antigen challenge in vivo","volume":"191","author":"Lloyd","year":"2000","journal-title":"J Exp Med"},{"key":"2022011223190606200_b11","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1159\/000072140","article-title":"Association of interleukin-5 and eotaxin with acute exacerbation of asthma","volume":"131","author":"Park","year":"2003","journal-title":"Int Arch Allergy Immunol"},{"key":"2022011223190606200_b12","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1046\/j.1365-2249.1998.00688.x","article-title":"Kinetics of eotaxin expression and its relationship to eosinophil accumulation and activation in bronchial biopsies and bronchoalveolar lavage (BAL) of asthmatic patients after allergen inhalation","volume":"114","author":"Brown","year":"1998","journal-title":"Clin Exp Immunol"},{"key":"2022011223190606200_b13","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1183\/09031936.98.11040821","article-title":"Increases in airway eosinophils and interleukin-5 with minimal bronchoconstriction during repeated low-dose allergen challenge in atopic asthmatics","volume":"11","author":"Sulakvelidze","year":"1998","journal-title":"Eur Respir J"},{"key":"2022011223190606200_b14","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1097\/00063198-200301000-00004","article-title":"Interleukin-13 in asthma","volume":"9","author":"Wills-Karp","year":"2003","journal-title":"Curr Opin Pulm Med"},{"key":"2022011223190606200_b15","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/S0738-081X(02)00369-3","article-title":"Animal models of atopic dermatitis","volume":"21","author":"Marsella","year":"2003","journal-title":"Clin Dermatol"},{"key":"2022011223190606200_b16","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/s11882-003-0015-8","article-title":"Animal models of allergic asthma","volume":"3","author":"Isenberg-Feig","year":"2003","journal-title":"Curr Allergy Asthma Rep"},{"key":"2022011223190606200_b17","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/j.1749-6632.2002.tb04139.x","article-title":"Food allergy animal models: an overview","volume":"964","author":"Helm","year":"2002","journal-title":"Ann N Y Acad Sci"},{"key":"2022011223190606200_b18","doi-asserted-by":"crossref","DOI":"10.1046\/j.1365-2249.1998.00477.x","article-title":"Effects of adjuvants on the immune response to allergens in a murine model of allergen inhalation: cholera toxin induces a Th1-like response to Bet v 1, the major birch pollen allergen","volume":"111","author":"Wiedermann","year":"1998","journal-title":"Clin Exp Immunol"},{"key":"2022011223190606200_b19","doi-asserted-by":"crossref","first-page":"12467","DOI":"10.1073\/pnas.93.22.12467","article-title":"Genetic mapping of a murine locus controlling development of T helper 1\/T helper 2 type responses","volume":"93","author":"Gorham","year":"1996","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022011223190606200_b20","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1159\/000235000","article-title":"Monoclonal antibodies against birch pollen allergens: characterization by immunoblotting and use for single-step affinity purification of the major allergen Bet v 1","volume":"90","author":"Jarolim","year":"1989","journal-title":"Int Arch Allergy Appl Immunol"},{"key":"2022011223190606200_b21","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0264-410X(03)00528-0","article-title":"Mucosal co-application of lactic acid bacteria and allergen induces counter-regulatory immune responses in a murine model of birch pollen allergy","volume":"22","author":"Repa","year":"2003","journal-title":"Vaccine"},{"key":"2022011223190606200_b22","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1046\/j.1365-2249.1997.d01-953.x","article-title":"Modulation of the allergic immune response in BALB\/c mice by subcutaneous injection of high doses of the dominant T cell epitope from the major birch pollen allergen Bet v 1","volume":"107","author":"Bauer","year":"1997","journal-title":"Clin Exp Immunol"},{"key":"2022011223190606200_b23","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1046\/j.0022-0477.2001.01214.x","article-title":"Mucosal tolerance as therapy of type I allergy: intranasal application of recombinant Bet v 1, the major birch pollen allergen, leads to the suppression of allergic immune responses and airway inflammation in sensitized mice","volume":"32","author":"Winkler","year":"2002","journal-title":"Clin Exp Allergy"},{"key":"2022011223190606200_b24","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1159\/000049496","article-title":"Intranasal treatment with a recombinant hypoallergenic derivative of the major birch pollen allergen Bet v 1 prevents allergic sensitization and airway inflammation in mice","volume":"126","author":"Wiedermann","year":"2001","journal-title":"Int Arch Allergy Immunol"},{"key":"2022011223190606200_b25","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1172\/JCI8624","article-title":"Th2 responses induced by epicutaneous or inhalational protein exposure are differentially dependent on IL-4","volume":"105","author":"Herrick","year":"2000","journal-title":"J Clin Invest"},{"key":"2022011223190606200_b26","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1159\/000053781","article-title":"The impact of the route and frequency of antigen exposure on the IgE response in allergy","volume":"124","author":"Nelde","year":"2001","journal-title":"Int Arch Allergy Immunol"},{"key":"2022011223190606200_b27","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.4049\/jimmunol.162.5.2477","article-title":"Effects of Th2 cytokines on chemokine expression in the lung: IL-13 potently induces eotaxin expression by airway epithelial cells","volume":"162","author":"Li","year":"1999","journal-title":"J Immunol"},{"key":"2022011223190606200_b28","doi-asserted-by":"crossref","first-page":"4788","DOI":"10.4049\/jimmunol.169.9.4788","article-title":"Long-lived Th2 memory in experimental allergic asthma","volume":"169","author":"Mojtabavi","year":"2002","journal-title":"J Immunol"},{"key":"2022011223190606200_b29","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1046\/j.1365-2133.2001.04179.x","article-title":"The role of cutaneous dendritic cells in the immunopathogenesis of atopic dermatitis","volume":"144","author":"Banfield","year":"2001","journal-title":"Br J Dermatol"},{"key":"2022011223190606200_b30","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0163-7258(03)00094-9","article-title":"Why are dendritic cells important in allergic diseases of the respiratory tract?","volume":"100","author":"Upham","year":"2003","journal-title":"Pharmacol Ther"},{"key":"2022011223190606200_b31","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/eji.1830230130","article-title":"Regulation of T helper cell cytokine expression: functional dichotomy of antigen-presenting cells","volume":"23","author":"Schmitz","year":"1993","journal-title":"Eur J Immunol"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2249.2004.02519.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/137\/1\/12\/42147153\/j.1365-2249.2004.02519.x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/137\/1\/12\/42147153\/j.1365-2249.2004.02519.x.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T21:20:19Z","timestamp":1682716819000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/137\/1\/12\/6458032"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,6,15]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2004,6,15]]},"published-print":{"date-parts":[[2004,6,15]]}},"URL":"https:\/\/doi.org\/10.1111\/j.1365-2249.2004.02519.x","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"value":"0009-9104","type":"print"},{"value":"1365-2249","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2004,7]]},"published":{"date-parts":[[2004,6,15]]}}}