{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T14:12:25Z","timestamp":1774620745728,"version":"3.50.1"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[1998,12,1]],"date-time":"1998-12-01T00:00:00Z","timestamp":912470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1998,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Airway hyperresponsiveness to inhalational challenge with methacholine (MCh) develops by 32 h after allergen challenge of actively sensitized BN rats. To test the hypothesis that CD4 + T cells mediate allergen-induced hyperresponsiveness independent of IgE-mediated mechanisms, we administered CD4 + T cells, CD8 + T cells, and a mixture of CD4 + and CD8 + T cells (total T cells) isolated from the cervical lymph nodes of rats sensitized with ovalbumin (OA) to naive BN rats that underwent aerosol challenge with either OA or bovine serum albumin (BSA) 2 d later. Responsiveness to MCh was measured 2 d before transfer of T cells and 32 h after challenge with OA or BSA. Airway responsiveness increased significantly in recipients of CD4 + T cells after OA challenge, but not in any other of the treatment groups. Analysis of bronchoalveolar lavage (BAL) cells for major basic protein expression by immunostaining showed eosinophilia in OA-challenged CD4 + and total T-cell recipients. Cells retrieved by bronchoalveolar lavage showed increased expression of IL-5 mRNA (in situ hybridization) in CD4 + T cell recipients after OA challenge compared with other groups. Interferon- \u03b3 mRNA was expressed to the greatest extent in CD8 + recipients, but it was elevated in both OA- and BSA-challenged animals. We conclude that CD4 + T cells can induce airway hyperresponsiveness after inhalational challenge with allergen and this is associated with IL-5 production and eosinophilia. CD8 + T cells may have a negative regulatory effect on responsiveness, possibly mediated by interferon- \u03b3.<\/jats:p>","DOI":"10.1164\/ajrccm.158.6.9709123","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T13:51:12Z","timestamp":1365083472000},"page":"1863-1870","source":"Crossref","is-referenced-by-count":27,"title":["CD4 + T Cells Can Induce Airway Hyperresponsiveness to Allergen Challenge in the Brown Norway Rat"],"prefix":"10.1093","volume":"158","author":[{"given":"HIDEYASU","family":"MISHIMA","sequence":"first","affiliation":[{"name":"Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University, and the Respiratory Health Network of Centres of Excellence, Montreal, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MASAYUKI","family":"HOJO","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University, and the Respiratory Health Network of Centres of Excellence, Montreal, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"AZUMA","family":"WATANABE","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University, and the Respiratory Health Network of Centres of Excellence, Montreal, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"QUTAYBA A.","family":"HAMID","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University, and the Respiratory Health Network of Centres of Excellence, Montreal, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JAMES G.","family":"MARTIN","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University, and the Respiratory Health Network of Centres of Excellence, Montreal, Quebec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1998,12,1]]},"reference":[{"key":"2026032709055963200_B1","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1164\/ajrccm\/136.3.600","article-title":"Allergen-induced recruitment of bronchoalveolar helper (OKT4) and suppressor (OKT8) T-cells in asthma. Relative increases in OKT8 cells in single early responders compared with those in late-phase responders.","volume":"136","author":"Gonzalez","year":"1987","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032709055963200_B2","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1056\/NEJM199201303260504","article-title":"Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma.","volume":"326","author":"Robinson","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"2026032709055963200_B3","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1164\/ajrccm\/141.2.407","article-title":"T lymphocytes and eosinophils in allergen-induced late-phase asthmatic reactions in the guinea pig.","volume":"141","author":"Frew","year":"1990","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032709055963200_B4","first-page":"591","article-title":"T-cells subsets and activation in bronchial mucosa of sensitized Brown-Norway rats after single allergen exposure.","volume":"85","author":"Haczku","year":"1995","journal-title":"Immunology"},{"key":"2026032709055963200_B5","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1365-2567.1996.tb00011.x","article-title":"Expression of Th-2 cytokines interleukin-4 and -5 and of Th-1 cytokine interferon-gamma in ovalbumin-exposed sensitized Brown-Norway rats.","volume":"88","author":"Haczku","year":"1996","journal-title":"Immunology"},{"key":"2026032709055963200_B6","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1172\/JCI115166","article-title":"Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma.","volume":"87","author":"Hamid","year":"1991","journal-title":"J. Clin. Invest."},{"key":"2026032709055963200_B7"},{"key":"2026032709055963200_B8","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/0091-6749(93)90085-T","article-title":"Eosinophil survival activity identified as interleukin-5 is associated with eosinophil recruitment and degranulation and lung injury twenty-four hours after segmental antigen lung challenge.","volume":"92","author":"Ohnishi","year":"1993","journal-title":"J. Allergy Clin. Immunol."},{"key":"2026032709055963200_B9","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.4049\/jimmunol.141.4.1218","article-title":"IgE production by normal human B cells induced by alloreactive T cell clones is mediated by IL-4 and suppressed by IFN-gamma.","volume":"141","author":"Pene","year":"1988","journal-title":"J. Immunol."},{"key":"2026032709055963200_B10","doi-asserted-by":"crossref","first-page":"592","DOI":"10.4049\/jimmunol.146.2.592","article-title":"Tumor necrosis factor combines with IL-4 or IFN-gamma to selectively enhance endothelial cell adhesiveness for T cells: the contribution of vascular cell adhesion molecule-1-dependent and -independent binding mechanisms.","volume":"146","author":"Thornhill","year":"1991","journal-title":"J. Immunol."},{"key":"2026032709055963200_B11","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.4049\/jimmunol.148.4.1086","article-title":"IL-4 induces adherence of human eosinophils and basophils but not neutrophils to endothelium: association with expression of VCAM-1.","volume":"148","author":"Schleimer","year":"1992","journal-title":"J. Immunol."},{"key":"2026032709055963200_B12","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1084\/jem.167.1.219","article-title":"Recombinant human interleukin 5 is a selective activator of human eosinophil function.","volume":"167","author":"Lopez","year":"1988","journal-title":"J. Exp. Med."},{"key":"2026032709055963200_B13","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1084\/jem.167.1.43","article-title":"Purified interleukin 5 supports the terminal differentiation and proliferation of murine eosinophilic precursors.","volume":"167","author":"Yamaguchi","year":"1988","journal-title":"J. Exp. Med."},{"key":"2026032709055963200_B14","first-page":"258","article-title":"IL-5 enhances the in vitro adhesion of human eosinophils, but not neutrophils, in a leucocyte integrin (CD11\/18)-dependent manner.","volume":"71","author":"Walsh","year":"1990","journal-title":"Immunology"},{"key":"2026032709055963200_B15","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1165\/ajrcmb\/9.4.356","article-title":"T cells are the principal source of interleukin-5 mRNA in allergen-induced rhinitis.","volume":"9","author":"Ying","year":"1993","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2026032709055963200_B16","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1165\/ajrcmb.10.5.8179909","article-title":"Interleukin-4, -5, and -6 and tumor necrosis factor-\u03b1 in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines.","volume":"10","author":"Bradding","year":"1994","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2026032709055963200_B17","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1084\/jem.179.2.703","article-title":"Interleukin 5 synthesis by eosinophils: association with granules and immunoglobulin-dependent secretion.","volume":"179","author":"Dubucquoi","year":"1994","journal-title":"J. Exp. Med."},{"key":"2026032709055963200_B18","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1164\/ajrccm\/137.5.1033","article-title":"Late airway responses to antigen challenge in sensitized inbred rats.","volume":"137","author":"Eidelman","year":"1988","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032709055963200_B19","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1164\/ajrccm\/148.4_Pt_1.932","article-title":"Effect of dexamethasone on airway inflammation and responsiveness after antigen challenge of the rat.","volume":"148","author":"Renzi","year":"1993","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032709055963200_B20","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1164\/ajrccm.152.1.7599864","article-title":"Adoptive transfer of allergic airway responses with sensitized lymphocytes in BN rats.","volume":"152","author":"Watanabe","year":"1995","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026032709055963200_B21","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1046\/j.1365-2567.1997.d01-2221.x","article-title":"Adoptive transfer of allergen-specific CD4+ T cells induces airway inflammation and hyperresponsiveness in brown-Norway rats.","volume":"91","author":"Haczku","year":"1997","journal-title":"Immunology"},{"key":"2026032709055963200_B22","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1172\/JCI118165","article-title":"Transfer of allergic airway responses with antigen-primed CD4+ but not CD8+ T cells in Brown Norway rats.","volume":"96","author":"Watanabe","year":"1995","journal-title":"J. Clin. Invest."},{"key":"2026032709055963200_B23","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1165\/ajrcmb.16.1.8998081","article-title":"Adoptively tranferred late allergic airway responses are associated with Th2-type cytokines in the rat.","volume":"16","author":"Watanabe","year":"1997","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2026032709055963200_B24","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1084\/jem.173.3.775","article-title":"Messenger RNA expression of the cytokine gene cluster, interleukin 3 (IL-3), IL-4, IL-5, and granulocyte\/macrophage colony-stimulating factor, in allergen-induced late-phase cutaneous reactions in atopic subjects.","volume":"173","author":"Kay","year":"1991","journal-title":"J. Exp. Med."},{"key":"2026032709055963200_B25","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/0091-6749(91)90253-K","article-title":"Characterization of allergen-induced bronchial hyperresponsiveness and airway inflammation in actively sensitized Brown-Norway rats.","volume":"88","author":"Elwood","year":"1991","journal-title":"J. Allergy Clin. Immunol."},{"key":"2026032709055963200_B26","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1159\/000236340","article-title":"Airway hyperresponsiveness is associated with inflammatory cell infiltration in Brown-Norway rats.","volume":"99","author":"Elwood","year":"1992","journal-title":"Int. Arch. Allergy Immunol."},{"key":"2026032709055963200_B27","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1164\/ajrccm\/145.6.1306","article-title":"Effect of acute and chronic antigen inhalation on airway morphology and responsiveness in actively sensitized rats.","volume":"145","author":"Kips","year":"1992","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032709055963200_B28","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1172\/JCI117032","article-title":"Alpha 4-integrins mediate antigen-induced late bronchial responses and prolonged airway hyperresponsiveness in sheep.","volume":"93","author":"Abraham","year":"1994","journal-title":"J. Clin. Invest."},{"key":"2026032709055963200_B29","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1165\/ajrcmb.10.6.8003337","article-title":"Depletion of murine CD4+ T lymphocytes prevents antigen-induced airway hyperreactivity and pulmonary eosinophilia.","volume":"10","author":"Gavett","year":"1994","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2026032709055963200_B30","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1164\/ajrccm\/145.6.1289","article-title":"Effect of dexamethasone and cyclosporin A on allergen-induced airway hyperresponsiveness and inflammatory cell responses in sensitized Brown-Norway rats.","volume":"145","author":"Elwood","year":"1992","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032709055963200_B31","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/S0091-6749(96)80157-6","article-title":"Effect of antigen provocation of IL-5 transgenic mice on eosinophil mobilization and bronchial hyperresponsiveness.","volume":"97","author":"Lefort","year":"1996","journal-title":"J. Allergy Clin. Immunol."},{"key":"2026032709055963200_B32","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1164\/ajrccm\/151.3_Pt_1.822","article-title":"Role of VLA-4 and LFA-1 in allergen-induced airway hyperresponsiveness and lung inflammation in the rat.","volume":"151","author":"Laberge","year":"1995","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026032709055963200_B33","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1084\/jem.180.3.795","article-title":"Antibody to very late activation antigen 4 prevents antigen-induced bronchial hyperreactivity and cellular infiltration in the guinea pig airways.","volume":"180","author":"Pretolani","year":"1994","journal-title":"J. Exp. Med."},{"key":"2026032709055963200_B34","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/BF00196101","article-title":"Therapeutic approaches to asthma based on VLA-4 integrin and its counter receptors.","volume":"16","author":"Metzger","year":"1995","journal-title":"Springer Semin. Immunopathol."},{"key":"2026032709055963200_B35","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1159\/000236679","article-title":"Contribution of intercellular-adhesion molecule-1 in allergen-induced airway hyperresponsiveness and inflammation in sensitised brown-Norway rats.","volume":"104","author":"Sun","year":"1994","journal-title":"Int. Arch. Allergy Immunol."},{"key":"2026032709055963200_B36","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1073\/pnas.94.4.1344","article-title":"Allergen-induced bronchial hyperreactivity and eosinophilic inflammation occur in the absence of IgE in a mouse model of asthma.","volume":"94","author":"Mehlhop","year":"1997","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026032709055963200_B37","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1084\/jem.168.2.543","article-title":"Lymphokine-mediated regulation of the proliferative response of clones of T helper 1 and T helper 2 cells.","volume":"168","author":"Fernandez-Botran","year":"1988","journal-title":"J. Exp. Med."},{"key":"2026032709055963200_B38","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.4049\/jimmunol.148.7.2142","article-title":"Reciprocal regulatory effects of IFN-gamma and IL-4 on the in vitro development of human Th1 and Th2 clones.","volume":"148","author":"Maggi","year":"1992","journal-title":"J. Immunol."},{"key":"2026032709055963200_B39","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1126\/science.3107127","article-title":"Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production.","volume":"236","author":"Snapper","year":"1987","journal-title":"Science"},{"key":"2026032709055963200_B40","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1164\/ajrccm\/148.6_Pt_1.1623","article-title":"Inhibitory effect of the TRFK-5 anti-IL-5 antibody in a guinea pig model of asthma: Part 1.","volume":"148","author":"Mauser","year":"1993","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032709055963200_B41","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1164\/ajrccm\/147.3.548","article-title":"Effect of anti-IL-5 and IL-5 on airway hyperreactivity and eosinophils in guinea pigs.","volume":"147","author":"Van Oosterhout","year":"1993","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032709055963200_B42","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1164\/ajrccm.152.2.7633694","article-title":"Effects of an antibody to interleukin-5 in a monkey model of asthma.","volume":"152","author":"Mauser","year":"1995","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026032709055963200_B43","doi-asserted-by":"crossref","first-page":"2680","DOI":"10.4049\/jimmunol.156.8.2680","article-title":"Mice lacking the IFN-gamma receptor have impaired ability to resolve a lung eosinophilic inflammatory response associated with a prolonged capacity of T cells to exhibit a Th2 cytokine profile.","volume":"156","author":"Coyle","year":"1996","journal-title":"J. Immunol."},{"key":"2026032709055963200_B44","doi-asserted-by":"crossref","first-page":"351","DOI":"10.4049\/jimmunol.152.1.351","article-title":"Inhibition of IgE production and normalization of airways responsiveness by sensitized CD8 T cells in a mouse model of allergen-induced sensitization.","volume":"152","author":"Renz","year":"1994","journal-title":"J. Immunol."}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/158\/6\/1863\/67432158\/ajrccm_158_6_1863.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/158\/6\/1863\/67432158\/ajrccm_158_6_1863.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T13:06:26Z","timestamp":1774616786000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/158\/6\/1863\/8530343"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,12,1]]},"references-count":44,"journal-issue":{"issue":"6","published-online":{"date-parts":[[1998,12,1]]},"published-print":{"date-parts":[[1998,12,1]]}},"URL":"https:\/\/doi.org\/10.1164\/ajrccm.158.6.9709123","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1998,12]]},"published":{"date-parts":[[1998,12,1]]}}}