{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T03:59:04Z","timestamp":1771473544782,"version":"3.50.1"},"reference-count":48,"publisher":"Rockefeller University Press","issue":"8","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,10,16]]},"abstract":"<jats:p>Interleukin (IL)-4 and IL-12 together with T cell receptor (TCR) engagement are crucial for the differentiation of CD4+ T cells into T helper (Th)2 or Th1 cells, respectively. Although IL-4 receptors (IL-4Rs) but not IL-12Rs are expressed on naive CD4+ T cells, IL-4 has no apparent advantage over IL-12 in driving naive T cell differentiation when the cells are primed with both IL-4 and IL-12 in vitro. It was found that IL-4\u2013induced phosphorylation of Janus kinases 1 and 3, IL-4R\u03b1, signal transducer and activator of transcription 6, and insulin receptor substrate 2 was strikingly but transiently inhibited by TCR ligation both in conventional and TCR transgenic T cells. TCR engagement also blocked the expression of an IL-4\u2013inducible gene. Signals induced by other cytokines, including IL-2, IL-6, and interferon \u03b1, but not by insulin-like growth factor 1, were also blocked by TCR engagement. The capacity of various inhibitors to reverse TCR-mediated inhibition of IL-4 signaling suggested that activation of the Ras\u2013mitogen-activated protein kinase pathway and of the calcineurin pathway contribute to desensitizing IL-4R. IL-4 responsiveness returned at about the time (\u223c12 h) that IL-12\u2013mediated signaling was first observed. Thus, through different mechanisms, neither IL-4R nor IL-12R has any clear advantage in polarizing cells; rather, the availability of cytokine is probably the limiting factor in this process.<\/jats:p>","DOI":"10.1084\/jem.192.8.1125","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"1125-1134","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":41,"title":["Transient Inhibition of Interleukin 4 Signaling by T Cell Receptor Ligation"],"prefix":"10.1084","volume":"192","author":[{"given":"Jinfang","family":"Zhu","sequence":"first","affiliation":[{"name":"aLaboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Huang","sequence":"additional","affiliation":[{"name":"aLaboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liying","family":"Guo","sequence":"additional","affiliation":[{"name":"aLaboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Stonehouse","sequence":"additional","affiliation":[{"name":"aLaboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia J.","family":"Watson","sequence":"additional","affiliation":[{"name":"aLaboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane","family":"Hu-Li","sequence":"additional","affiliation":[{"name":"aLaboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William E.","family":"Paul","sequence":"additional","affiliation":[{"name":"aLaboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2000,10,9]]},"reference":[{"key":"2023072509343185800_R1","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1146\/annurev.iy.12.040194.003223","article-title":"Acquisition of lymphokine-producing phenotype by CD4+ T cells","volume":"12","author":"Seder","year":"1994","journal-title":"Annu. 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