{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T18:28:22Z","timestamp":1791138502269,"version":"4.1.0"},"reference-count":42,"publisher":"Rockefeller University Press","issue":"7","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,4,2]]},"abstract":"<jats:p>T cells secreting interleukin (IL)-4 and IL-5 (T helper cell type 2 [Th2] cells) play a detrimental role in a variety of diseases, but specific methods of regulating their activity remain elusive. T1\/ST2 is a surface ligand of the IL-1 receptor family, expressed on Th2- but not on interferon (IFN)-\u03b3\u2013producing Th1 cells. Prior exposure of BALB\/c mice to the attachment (G) or fusion (F) protein of respiratory syncytial virus (RSV) increases illness severity during intranasal RSV challenge, due to Th2-driven lung eosinophilia and exuberant Th1-driven pulmonary infiltration, respectively. We used these polar models of viral illness to study the recruitment of T1\/ST2 cells to the lung and to test the effects of anti-T1\/ST2 treatment in vivo. T1\/ST2 was present on a subset of CD4+ cells from mice with eosinophilic lung disease. Monoclonal anti-T1\/ST2 treatment reduced lung inflammation and the severity of illness in mice with Th2 (but not Th1) immunopathology. These results show that inhibition of T1\/ST2 has a specific effect on virally induced Th2 responses and suggests that therapy targeted at this receptor might be of value in treating Th2-driven illness.<\/jats:p>","DOI":"10.1084\/jem.193.7.785","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"785-792","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":97,"title":["Inhibition of T1\/St2 during Respiratory Syncytial Virus Infection Prevents T Helper Cell Type 2 (Th2)- but Not Th1-Driven Immunopathology"],"prefix":"10.1084","volume":"193","author":[{"given":"Gerhard","family":"Walzl","sequence":"first","affiliation":[{"name":"aDepartment of Respiratory Medicine, National Heart and Lung Institute at St. Mary's Hospital, Imperial College of Science, Technology and Medicine, London W2 1PG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Matthews","sequence":"additional","affiliation":[{"name":"aDepartment of Respiratory Medicine, National Heart and Lung Institute at St. Mary's Hospital, Imperial College of Science, Technology and Medicine, London W2 1PG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Kendall","sequence":"additional","affiliation":[{"name":"aDepartment of Respiratory Medicine, National Heart and Lung Institute at St. Mary's Hospital, Imperial College of Science, Technology and Medicine, London W2 1PG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Carlos","family":"Gutierrez-Ramos","sequence":"additional","affiliation":[{"name":"bDepartment of Biology, Inflammation Division, Millennium Pharmaceuticals, Incorporated, Cambridge, Massachusetts 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Coyle","sequence":"additional","affiliation":[{"name":"bDepartment of Biology, Inflammation Division, Millennium Pharmaceuticals, Incorporated, Cambridge, Massachusetts 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.M.","family":"Openshaw","sequence":"additional","affiliation":[{"name":"aDepartment of Respiratory Medicine, National Heart and Lung Institute at St. Mary's Hospital, Imperial College of Science, Technology and Medicine, London W2 1PG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Hussell","sequence":"additional","affiliation":[{"name":"aDepartment of Respiratory Medicine, National Heart and Lung Institute at St. Mary's Hospital, Imperial College of Science, Technology and Medicine, London W2 1PG, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2001,3,26]]},"reference":[{"key":"2023072509435895000_R1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1146\/annurev.iy.10.040192.002125","article-title":"Regulation of immunity to parasites by T cells and T cell-derived cytokines","volume":"10","author":"Sher","year":"1992","journal-title":"Annu. Rev. Immunol."},{"key":"2023072509435895000_R2","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/383787a0","article-title":"Functional diversity of helper T lymphocytes","volume":"383","author":"Abbas","year":"1996","journal-title":"Nature."},{"key":"2023072509435895000_R3","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/0167-5699(96)80606-2","article-title":"The expanding universe of T-cell subsetsTh1, Th2 and more","volume":"17","author":"Mosmann","year":"1996","journal-title":"Immunol. Today."},{"key":"2023072509435895000_R4","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1084\/jem.187.1.129","article-title":"Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s","volume":"187","author":"Bonecchi","year":"1998","journal-title":"J. Exp. Med."},{"key":"2023072509435895000_R5","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/34814","article-title":"CCR5 is characteristic of Th1 lymphocytes","volume":"391","author":"Loetscher","year":"1998","journal-title":"Nature."},{"key":"2023072509435895000_R6","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1084\/jem.188.8.1485","article-title":"Selective expression and functions of interleukin 18 receptor on T helper (Th) type 1 but not Th2 cells","volume":"188","author":"Xu","year":"1998","journal-title":"J. Exp. Med."},{"key":"2023072509435895000_R7","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S0092-8674(00)81299-4","article-title":"The proto-oncogene c-maf is responsible for tissue-specific expression of interleukin-4","volume":"85","author":"Ho","year":"1996","journal-title":"Cell."},{"key":"2023072509435895000_R8","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/S0092-8674(00)80240-8","article-title":"The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells","volume":"89","author":"Zheng","year":"1997","journal-title":"Cell."},{"key":"2023072509435895000_R9","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1084\/jem.187.6.875","article-title":"Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes","volume":"187","author":"Sallusto","year":"1998","journal-title":"J. Exp. Med."},{"key":"2023072509435895000_R10","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1126\/science.277.5334.2005","article-title":"Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells","volume":"277","author":"Sallusto","year":"1997","journal-title":"Science."},{"key":"2023072509435895000_R11","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1084\/jem.190.7.895","article-title":"Crucial role of the interleukin 1 receptor family member T1\/ST2 in T helper cell type 2\u2013mediated lung mucosal immune responses","volume":"190","author":"Coyle","year":"1999","journal-title":"J. Exp. Med."},{"key":"2023072509435895000_R12","doi-asserted-by":"crossref","first-page":"3621","DOI":"10.1002\/(SICI)1521-4141(199911)29:11<3621::AID-IMMU3621>3.0.CO;2-Z","article-title":"Expression of Th2 cytokines and the stable Th2 marker ST2L in the absence of IL-4 during Leishmania major infection","volume":"29","author":"Kropf","year":"1999","journal-title":"Eur. J. Immunol."},{"key":"2023072509435895000_R13","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1084\/jem.187.5.787","article-title":"Selective expression of a stable cell surface molecule on type 2 but not type 1 helper T cells","volume":"187","author":"Xu","year":"1998","journal-title":"J. Exp. Med."},{"key":"2023072509435895000_R14","doi-asserted-by":"crossref","first-page":"3882","DOI":"10.4049\/jimmunol.162.7.3882","article-title":"T1\/ST2 expression is enhanced on CD4+ T cells from schistosome egg-induced granulomasanalysis of Th cell cytokine coexpression ex vivo","volume":"162","author":"Lohning","year":"1999","journal-title":"J. Immunol."},{"key":"2023072509435895000_R15","doi-asserted-by":"crossref","first-page":"6930","DOI":"10.1073\/pnas.95.12.6930","article-title":"T1\/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function","volume":"95","author":"Lohning","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072509435895000_R16","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1172\/JCI824","article-title":"A multidrug-resistance protein (MRP)-like transmembrane pump is highly expressed by resting murine T helper (Th) 2, but not Th1 cells, and is induced to equal expression levels in Th1 and Th2 cells after antigenic stimulation in vivo","volume":"101","author":"Lohoff","year":"1998","journal-title":"J. Clin. Invest."},{"key":"2023072509435895000_R17","doi-asserted-by":"crossref","first-page":"754","DOI":"10.4049\/jimmunol.164.2.754","article-title":"The multidrug resistance protein 1a functionally important activation marker for murine Th1 cells","volume":"164","author":"Prechtl","year":"2000","journal-title":"J. Immunol."},{"key":"2023072509435895000_R18","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.4049\/jimmunol.162.3.1278","article-title":"Selective expression of a novel surface molecule by human Th2 cells in vivo","volume":"162","author":"Nagata","year":"1999","journal-title":"J. Immunol."},{"key":"2023072509435895000_R19","first-page":"609","article-title":"T1, an immunoglobulin superfamily member, is expressed in H-ras-dependent epithelial tumours of mammary cells","volume":"8","author":"Rossler","year":"1993","journal-title":"Oncogene."},{"key":"2023072509435895000_R20","doi-asserted-by":"crossref","first-page":"5708","DOI":"10.1073\/pnas.86.15.5708","article-title":"Serum- and oncoprotein-mediated induction of a gene with sequence similarity to the gene encoding carcinoembryonic antigen","volume":"86","author":"Klemenz","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072509435895000_R21","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/0014-5793(93)81333-U","article-title":"Presence of a novel primary response gene ST2L, encoding a product highly similar to the interleukin 1 receptor type 1","volume":"318","author":"Yanagisawa","year":"1993","journal-title":"FEBS Lett."},{"key":"2023072509435895000_R22","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1006\/dbio.1995.1063","article-title":"Secreted and membrane-bound isoforms of T1, an orphan receptor related to IL-1-binding proteins, are differently expressed in vivo","volume":"168","author":"Rossler","year":"1995","journal-title":"Dev. Biol."},{"key":"2023072509435895000_R23","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1002\/j.1460-2075.1994.tb06367.x","article-title":"Alternative promoter usage of the Fos-responsive gene Fit-1 generates mRNA isoforms coding for either secreted or membrane-bound proteins related to the IL-1 receptor","volume":"13","author":"Bergers","year":"1994","journal-title":"EMBO (Eur. Mol. Biol. Organ.) J."},{"key":"2023072509435895000_R24","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1084\/jem.191.6.1069","article-title":"T1\/ST2-deficient mice demonstrate the importance of T1\/ST2 in developing primary T helper cell type 2 responses","volume":"191","author":"Townsend","year":"2000","journal-title":"J. Exp. Med."},{"key":"2023072509435895000_R25","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1084\/jem.190.10.1541","article-title":"The absence of IL-1R\u2013related T1\/ST2 does not affect T helper cell type 2 development and its effector function","volume":"190","author":"Hoshino","year":"1999","journal-title":"J. Exp. Med."},{"key":"2023072509435895000_R26","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1002\/1521-4141(200007)30:7<1929::AID-IMMU1929>3.0.CO;2-1","article-title":"T1-deficient and T1-Fc-transgenic mice develop a normal protective Th2-type immune response following infection with Nippostrongylus brasiliensis","volume":"30","author":"Senn","year":"2000","journal-title":"Eur. J. Immunol."},{"key":"2023072509435895000_R27","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/S0022-3476(99)70079-X","article-title":"Respiratory syncytial virus and subsequent lower respiratory tract infections in developing countriesa new twist to an old virus","volume":"135","author":"Simoes","year":"1999","journal-title":"J. Pediatr."},{"key":"2023072509435895000_R28","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1542\/peds.95.4.500","article-title":"Asthma and immunoglobulin E antibodies after respiratory syncytial virus bronchiolitisa prospective cohort study with matched controls","volume":"95","author":"Sigurs","year":"1995","journal-title":"Pediatrics."},{"key":"2023072509435895000_R29","first-page":"94","article-title":"Immunopathologic mechanisms in lower respiratory tract disease of infants due to respiratory syncytial virus","volume":"26","author":"McIntosh","year":"1980","journal-title":"Prog. Med. Virol."},{"key":"2023072509435895000_R30","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1542\/peds.90.1.137","article-title":"Serious respiratory tract disease caused by respiratory syncytial virusprospects for improved therapy and effective immunization","volume":"90","author":"Chanock","year":"1992","journal-title":"Pediatrics."},{"key":"2023072509435895000_R31","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1084\/jem.179.1.81","article-title":"Distinct types of lung disease caused by functional subsets of antiviral T cells","volume":"179","author":"Alwan","year":"1994","journal-title":"J. Exp. Med."},{"key":"2023072509435895000_R32","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/0264-410X(93)90284-5","article-title":"Distinct patterns of T and B cell immunity to respiratory syncytial virus induced by individual proteins","volume":"11","author":"Alwan","year":"1993","journal-title":"Vaccine."},{"key":"2023072509435895000_R33","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1128\/jvi.56.1.55-59.1985","article-title":"Cytotoxic T-cell response to respiratory syncytial virus in mice","volume":"56","author":"Bangham","year":"1985","journal-title":"J. Virol."},{"key":"2023072509435895000_R34","doi-asserted-by":"crossref","first-page":"328","DOI":"10.4049\/jimmunol.159.1.328","article-title":"IL-12 treatment attenuates Th2 and B cell responses but does not improve vaccine-enhanced lung illness","volume":"159","author":"Hussell","year":"1997","journal-title":"J. Immunol."},{"key":"2023072509435895000_R35","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1099\/0022-1317-77-10-2447","article-title":"Th1 and Th2 cytokine induction in pulmonary T-cells during infection with respiratory syncytial virus","volume":"77","author":"Hussell","year":"1996","journal-title":"J. Gen. Virol."},{"key":"2023072509435895000_R36","doi-asserted-by":"crossref","first-page":"3341","DOI":"10.1002\/eji.1830271233","article-title":"CD8+ T-cells control Th2-driven pathology during pulmonary respiratory syncytial virus infection","volume":"27","author":"Hussell","year":"1997","journal-title":"Eur. J. Immunol."},{"key":"2023072509435895000_R37","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1172\/JCI8107","article-title":"Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation","volume":"106","author":"Lambrecht","year":"2000","journal-title":"J. Clin. Invest."},{"key":"2023072509435895000_R38","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1093\/infdis\/168.1.47","article-title":"Infection of monocytes during measles","volume":"168","author":"Esolen","year":"1993","journal-title":"J. Infect. Dis."},{"key":"2023072509435895000_R39","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1084\/jem.187.9.1517","article-title":"Challenging cytokine redundancyinflammatory cell movement and clinical course of experimental autoimmune encephalomyelitis are normal in lymphotoxin-deficient, but not tumor necrosis factor-deficient, mice","volume":"187","author":"Sean","year":"1998","journal-title":"J. Exp. Med."},{"key":"2023072509435895000_R40","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/S0167-5699(99)01573-X","article-title":"Tumor necrosis factora master-regulator of leukocyte movement","volume":"21","author":"Sedgwick","year":"2000","journal-title":"Immunol. Today."},{"key":"2023072509435895000_R41","doi-asserted-by":"crossref","first-page":"5411","DOI":"10.4049\/jimmunol.154.10.5411","article-title":"TNF-alpha mediates recruitment of neutrophils and eosinophils during airway inflammation","volume":"154","author":"Lukacs","year":"1995","journal-title":"J. Immunol."},{"key":"2023072509435895000_R42","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1074\/jbc.271.1.124","article-title":"Transcription of the interleukin-1 receptor-related T1 gene is initiated at different promoters in mast cells and fibroblasts","volume":"271","author":"Gachter","year":"1996","journal-title":"J. Biol. Chem."}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/193\/7\/785\/1702127\/002052.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/193\/7\/785\/1702127\/002052.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T10:54:28Z","timestamp":1690282468000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/193\/7\/785\/25953\/Inhibition-of-T1-St2-during-Respiratory-Syncytial"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,3,26]]},"references-count":42,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2001,4,2]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.193.7.785","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,3,26]]}}}