{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T14:03:12Z","timestamp":1776348192124,"version":"3.51.2"},"reference-count":30,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,5,11]]},"abstract":"<jats:p>Interleukin (IL)-4 is the quintessential T helper type 2 (Th2) cytokine produced by CD4+ T cells in response to helminth infection. IL-4 not only promotes the differentiation of Th2 cells but is also critical for immunoglobulin (Ig) G1 and IgE isotype-switched antibody responses. Despite the IL-4\u2013mediated link between Th2 cells and B lymphocytes, the location of IL-4\u2013producing T cells in the lymph nodes is currently unclear. Using IL-4 dual reporter mice, we examined the Th2 response and IL-4 production in the draining mesenteric lymph nodes during infection with the enteric nematode Heligmosomoides polygyrus. We show that although IL-4\u2013competent Th2 cells are found throughout the B and T cell areas, IL-4\u2013producing Th2 cells are restricted to the B cell follicles and associate with germinal centers. Consistent with their localization, IL-4 producers express high levels of CXCR5, ICOS, PD-1, IL-21, and BCL-6, a phenotype characteristic of T follicular helper (Tfh) cells. Although IL-4 was dispensable for the generation of Th2 and Tfh cells, its deletion resulted in defective B cell expansion and maturation. Our report reveals the compartmentalization of Th2 priming and IL-4 production in the lymph nodes during infection, and identifies Tfh cells as the dominant source of IL-4 in vivo.<\/jats:p>","DOI":"10.1084\/jem.20090313","type":"journal-article","created":{"date-parts":[[2009,5,11]],"date-time":"2009-05-11T14:43:39Z","timestamp":1242053019000},"page":"1001-1007","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":328,"title":["IL-4\u2013producing CD4+ T cells in reactive lymph nodes during helminth infection are T follicular helper cells"],"prefix":"10.1084","volume":"206","author":[{"given":"Irah L.","family":"King","sequence":"first","affiliation":[{"name":"Trudeau Institute, Saranac Lake, NY 12983"}]},{"given":"Markus","family":"Mohrs","sequence":"additional","affiliation":[{"name":"Trudeau Institute, Saranac Lake, NY 12983"}]}],"member":"291","published-online":{"date-parts":[[2009,4,20]]},"reference":[{"key":"2023072919540730100_bib1","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":"2023072919540730100_bib2","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1084\/jem.155.3.914","article-title":"Identification of a T cell\u2013derived b cell growth factor distinct from interleukin 2","volume":"155","author":"Howard","year":"1982","journal-title":"J. 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