{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T06:49:47Z","timestamp":1763016587808},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2005,11,18]],"date-time":"2005-11-18T00:00:00Z","timestamp":1132272000000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Scand J Immunol"],"published-print":{"date-parts":[[2005,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In subjects not developing allergy, inhalation of nonpathogenic protein antigens causes no harm and is associated with tolerance induction. Repeated exposure to aerosolized ovalbumin (OVA) likewise does not evoke airway inflammation and induces inhalation tolerance in experimental animals. The present study explored the role of the inhibitory T\u2010cell receptor CTLA\u20104, in preventing inflammation and in establishing inhalation tolerance in response to a protein antigen. Naive BALB\/<jats:italic>c<\/jats:italic> mice were injected intraperitoneally with anti\u2010CTLA\u20104 monoclonal antibody or control immunoglobulin G (IgG) and exposed daily to aerosolized saline or OVA over 10 or 20 consecutive days. OVA\u2010specific IgE levels and the inflammatory response in airway tissues were assessed 2 days after last exposure. The OVA\u2010specific IgE response was also evaluated in mice subjected to a subsequent immunogenic OVA challenge 18 days after last aerosol exposure. Additional mice were made tolerant by 10 days of OVA aerosol exposure and were then subjected to an immunogenic OVA challenge combined with CTLA\u20104 blockade or control IgG treatment. Repeated inhalation of aerosolized OVA alone did not cause a pulmonary inflammatory response. In contrast, 10 days of OVA exposure combined with blockade of CTLA\u20104 led to development of eosinophilic lung infiltrates, BAL fluid eosinophilia, goblet cell hyperplasia and increased OVA\u2010specific IgE. By 20 days of OVA exposure and blockade of CTLA\u20104, the inflammatory response remained. Mice exposed to aerosolized OVA for 10 days exhibited greatly reduced OVA\u2010specific IgE responses to subsequent immunogenic OVA challenge. Blockade of CTLA\u20104 during the period of OVA aerosol exposure did not prevent this suppression of the OVA\u2010specific IgE response. Neither did blockade of CTLA\u20104 during immunogenic OVA challenge alter the allergen\u2010specific IgE response. Our results indicate that <jats:italic>in vivo<\/jats:italic> blockade of CTLA\u20104 modulates the initial immune response to a protein antigen allowing the development of allergen\u2010induced airway inflammation in naive mice. However, this initial exaggerated immune response is followed by the induction of inhalation tolerance, demonstrating that CTLA\u20104 signalling is not decisive in this process. Our findings also show that once inhalation tolerance is established it may not be disrupted by blockade of CTLA\u20104.<\/jats:p>","DOI":"10.1111\/j.1365-3083.2005.01682.x","type":"journal-article","created":{"date-parts":[[2005,11,18]],"date-time":"2005-11-18T09:50:32Z","timestamp":1132307432000},"page":"437-444","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Blockade of CTLA\u20104 Promotes Airway Inflammation in Naive Mice Exposed to Aerosolized Allergen but Fails to Prevent Inhalation Tolerance"],"prefix":"10.1111","volume":"62","author":[{"given":"L.","family":"Alenmyr","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Matheu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Uller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Greiff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Malm\u2010Erjef\u00e4lt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.\u2010G.","family":"Ljunggren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. 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