{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:32:42Z","timestamp":1791451962531,"version":"4.3.3"},"reference-count":42,"publisher":"Rockefeller University Press","issue":"10","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,5,17]]},"abstract":"<jats:p>Using a single vector targeting strategy, we have generated mice with a combined deficiency of interleukin (IL)-4 and IL-13 to clarify their roles in T helper type 2 (Th2) cell responses. Using immunological challenges normally characterized by a Th2-like response, we have compared the responses of the double-deficient mice with those generated by wild-type, IL-4\u2013deficient, and IL-13\u2013deficient mice. Using a pulmonary granuloma model, induced with Schistosoma mansoni eggs, we demonstrate that although eosinophil infiltration, immunoglobulin E, and IL-5 production are reduced in the IL-4\u2013deficient mice and IL-13\u2013deficient mice, they are abolished only in the combined absence of both cytokines. Furthermore, IL-4\/13\u2013deficient animals are severely impaired in their ability to expel the gastrointestinal nematode Nippostrongylus brasiliensis. Unexpectedly, N. brasiliensis\u2013infected IL-4\/13\u2013deficient mice developed elevated IL-5 and eosinophilia, indicating that compensatory mechanisms exist for the expression of IL-5, although serum IgE remained undetectable. IL-4\/13\u2013deficient mice default to a Th1-like phenotype characterized by the expression of interferon \u03b3 and the production of IgG2a and IgG2b. We conclude that IL-4 and IL-13 cooperate to initiate rapid Th2 cell\u2013driven responses, and that although their functions overlap, they perform additive roles.<\/jats:p>","DOI":"10.1084\/jem.189.10.1565","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:49:30Z","timestamp":1027702170000},"page":"1565-1572","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":277,"title":["Simultaneous Disruption of Interleukin (IL)-4 and IL-13 Defines Individual Roles in T Helper Cell Type 2\u2013mediated Responses"],"prefix":"10.1084","volume":"189","author":[{"given":"Grahame J.","family":"McKenzie","sequence":"first","affiliation":[{"name":"From the *Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom; the \u2021Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom; and the \u00a7School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padraic G.","family":"Fallon","sequence":"additional","affiliation":[{"name":"From the *Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom; the \u2021Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom; and the \u00a7School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire L.","family":"Emson","sequence":"additional","affiliation":[{"name":"From the *Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom; the \u2021Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom; and the \u00a7School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard K.","family":"Grencis","sequence":"additional","affiliation":[{"name":"From the *Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom; the \u2021Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom; and the \u00a7School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew N.J.","family":"McKenzie","sequence":"additional","affiliation":[{"name":"From the *Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom; the \u2021Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom; and the \u00a7School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1999,5,17]]},"reference":[{"key":"2023072508203589000_B1","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1126\/science.1948049","article-title":"Generation and analysis of interleukin-4-deficient mice","volume":"254","author":"Kuhn","year":"1991","journal-title":"Science"},{"key":"2023072508203589000_B2","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/362245a0","article-title":"Disruption of the murine IL-4 gene blocks Th2 cytokine responses","volume":"362","author":"Kopf","year":"1993","journal-title":"Nature"},{"key":"2023072508203589000_B3","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/S0960-9822(98)70256-8","article-title":"Differences between IL-4R\u03b1-deficient and IL-4-deficient mice reveal a role for IL-13 in the regulation of Th2 responses","volume":"8","author":"Barner","year":"1998","journal-title":"Curr Biol"},{"key":"2023072508203589000_B4","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/380630a0","article-title":"Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene","volume":"380","author":"Shimoda","year":"1996","journal-title":"Nature"},{"key":"2023072508203589000_B5","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/380627a0","article-title":"Essential role of Stat6 in IL-4 signalling","volume":"380","author":"Takeda","year":"1996","journal-title":"Nature"},{"key":"2023072508203589000_B6","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S1074-7613(00)80439-2","article-title":"Stat6 is required for mediating responses to IL-4 and for the development of Th2 cells","volume":"4","author":"Kaplan","year":"1996","journal-title":"Immunity"},{"key":"2023072508203589000_B7","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S1074-7613(00)80625-1","article-title":"Impaired development of Th2 cells in IL-13-deficient mice","volume":"9","author":"McKenzie","year":"1998","journal-title":"Immunity"},{"key":"2023072508203589000_B8","doi-asserted-by":"crossref","first-page":"679","DOI":"10.4049\/jimmunol.142.2.679","article-title":"A family of small inducible proteins secreted by leukocytes are members of a new super-family that includes leukocyte and fibroblast-derived inflammatory agents, growth factors and indicators of various activation processes","volume":"142","author":"Brown","year":"1989","journal-title":"J Immunol"},{"key":"2023072508203589000_B9","first-page":"429","article-title":"TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties","volume":"5","author":"Mosmann","year":"1989","journal-title":"Annu Rev Immunol"},{"key":"2023072508203589000_B10","doi-asserted-by":"crossref","first-page":"3735","DOI":"10.1073\/pnas.90.8.3735","article-title":"Interleukin-13, a T-cell-derived cytokine that regulates human monocyte and B-cell function","volume":"90","author":"McKenzie","year":"1993","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072508203589000_B11","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1084\/jem.181.4.1373","article-title":"Activated mast cells produce interleukin 13","volume":"181","author":"Burd","year":"1995","journal-title":"J Exp Med"},{"key":"2023072508203589000_B12","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":"2023072508203589000_B13","doi-asserted-by":"crossref","first-page":"7151","DOI":"10.4049\/jimmunol.151.12.7151","article-title":"Modulation of murine macrophage function by IL-13","volume":"151","author":"Doherty","year":"1993","journal-title":"J Immunol"},{"key":"2023072508203589000_B14","doi-asserted-by":"crossref","first-page":"6370","DOI":"10.4049\/jimmunol.151.11.6370","article-title":"Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes","volume":"151","author":"de Waal Malefyt, R., C. 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