{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:31:49Z","timestamp":1791228709815,"version":"4.1.0"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2000,3,1]],"date-time":"2000-03-01T00:00:00Z","timestamp":951868800000},"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":[[2000,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The concept that IL-4 is the primary signal for Th2 lymphocyte differentiation has recently been put in doubt by studies in which the production of Th2-associated cytokines was detected in mice deficient in IL-4 synthesis or IL-4R triggering. In this study, we formally demonstrate by single cell analysis that CD4+ lymphocytes with a classical Th2 phenotype (IL-4+, IL-5+, IFN-\u03b3\u2212, IL-2\u2212) develop in significant numbers in helminth-infected mice deficient in either IL-4R \u03b1-chain or Stat6. While an expanded population of Th1 (IL-4\u2212, IL-5\u2212, IFN-\u03b3+, IL-2+) lymphocytes was observed in the same animals, surprisingly, cells with a mixed Th0 cytokine pattern were rare. The cytokine production phenotypes of the Th1 and Th2 subpopulations generated in infected Stat6-deficient mice were unaffected by in vitro neutralization of endogenous IL-4 or IFN-\u03b3. Nevertheless, while addition of exogenous rIL-12 resulted in transitory IFN-\u03b3 production by Th2 lymphocytes from both wild-type and Stat6-deficient mice, IL-4 synthesis was preserved in the former, but temporarily ablated in the latter cells. Importantly, IL-4+ IFN-\u03b3\u2212 and IL-4\u2212 IFN-\u03b3+ populations similar to those arising in helminth-infected Stat6-deficient mice could also be generated in vitro by repetitive polyclonal stimulation of CD4+CD62Lhigh lymphocytes from uninfected mice of the same strain. Together, the results of these single cell analysis experiments demonstrate that IL-4R\/Stat6 signaling, while influencing the final frequency of Th2 lymphocytes, is not essential for Th2 cell development, and suggest that this pathway has a previously unrecognized function in stabilizing Th2 populations once they have emerged.<\/jats:p>","DOI":"10.4049\/jimmunol.164.6.3047","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T16:28:33Z","timestamp":1398184113000},"page":"3047-3055","source":"Crossref","is-referenced-by-count":176,"title":["Single Cell Analysis Reveals That IL-4 Receptor\/Stat6 Signaling Is Not Required for the In Vivo or In Vitro Development of CD4+ Lymphocytes with a Th2 Cytokine Profile"],"prefix":"10.1093","volume":"164","author":[{"given":"Dragana","family":"Jankovic","sequence":"first","affiliation":[{"name":"Immunobiology Section, Laboratory of Parasitic Diseases , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika C","family":"Kullberg","sequence":"additional","affiliation":[{"name":"Immunobiology Section, Laboratory of Parasitic Diseases , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Noben-Trauth","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":"Patricia","family":"Caspar","sequence":"additional","affiliation":[{"name":"Immunobiology Section, Laboratory of Parasitic Diseases , 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"}]},{"given":"Alan","family":"Sher","sequence":"additional","affiliation":[{"name":"Immunobiology Section, Laboratory of Parasitic Diseases , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2000,3,15]]},"reference":[{"key":"2026020213193612800_R1","first-page":"787","volume-title":"Nature","year":"1996"},{"key":"2026020213193612800_R2","first-page":"174","volume-title":"Nature","year":"1996"},{"key":"2026020213193612800_R3","first-page":"171","volume-title":"Nature","year":"1996"},{"key":"2026020213193612800_R4","first-page":"313","volume-title":"Immunity","year":"1996"},{"key":"2026020213193612800_R5","first-page":"630","volume-title":"Nature","year":"1996"},{"key":"2026020213193612800_R6","first-page":"627","volume-title":"Nature","year":"1996"},{"key":"2026020213193612800_R7","first-page":"275","volume-title":"Immunity","year":"1998"},{"key":"2026020213193612800_R8","first-page":"547","volume-title":"Science","year":"1993"},{"key":"2026020213193612800_R9","first-page":"1119","volume-title":"Int. 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