{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:57:37Z","timestamp":1791424657590,"version":"4.3.3"},"reference-count":38,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,9,19]]},"abstract":"<jats:p>T cell receptor (TCR) signaling plays an important role in early interleukin (IL)-4 production by naive CD4+ T cells. This \u201cantigen-stimulated\u201d early IL-4 is sufficient for in vitro Th2 differentiation. Here, we provide evidence that early IL-4 production by naive CD4+ T cells stimulated with cognate peptide requires TCR-induced early GATA-3 expression and IL-2 receptor signaling, both of which are controlled by the degree of activation of extracellular signal-regulated kinase (ERK). Stimulation of naive CD4+ T cells from TCR transgenic mice with low concentrations of peptide-induced IL-2\u2013dependent STAT5 phosphorylation, IL-4-independent early GATA-3 expression, and IL-4 production. Neutralization of IL-2 abolished early IL-4 production without affecting early GATA-3 expression. In addition, naive CD4+ T cells from GATA-3 conditional KO mice failed to produce early IL-4 in response to TCR\/CD28 stimulation. Stimulation with high concentrations of peptide abrogated early GATA-3 expression and IL-2\u2013dependent STAT5 phosphorylation, and resulted in the failure to produce early IL-4. This high concentration\u2013mediated suppression of early IL-4 production was reversed by blockade of the ERK pathway. A MEK inhibition rescued early GATA-3 expression and responsiveness to IL-2; these cells were now capable of producing early IL-4 and undergoing subsequent Th2 differentiation.<\/jats:p>","DOI":"10.1084\/jem.20051304","type":"journal-article","created":{"date-parts":[[2005,9,19]],"date-time":"2005-09-19T19:18:07Z","timestamp":1127157487000},"page":"793-804","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":242,"title":["Independent roles for IL-2 and GATA-3 in stimulating naive CD4+ T cells to generate a Th2-inducing cytokine environment"],"prefix":"10.1084","volume":"202","author":[{"given":"Hidehiro","family":"Yamane","sequence":"first","affiliation":[{"name":"Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E.","family":"Paul","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2005,9,19]]},"reference":[{"key":"2023072513183339200_BIB1","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1084\/jem.172.3.921","volume":"172","year":"1990","journal-title":"J. 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Immunol."},{"key":"2023072513183339200_BIB19","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/S1074-7613(00)80671-8","volume":"9","year":"1998","journal-title":"Immunity."},{"key":"2023072513183339200_BIB20","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/S0092-8674(00)80240-8","volume":"89","year":"1997","journal-title":"Cell."},{"key":"2023072513183339200_BIB21","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/S1074-7613(00)80122-3","volume":"11","year":"1999","journal-title":"Immunity."},{"key":"2023072513183339200_BIB22","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1038\/ni1128","volume":"5","year":"2004","journal-title":"Nat. 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