{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T08:30:53Z","timestamp":1770366653294,"version":"3.49.0"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2003,8,1]],"date-time":"2003-08-01T00:00:00Z","timestamp":1059696000000},"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":[[2003,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In the present study we demonstrate that all CD4+ T cells in human tonsil expressing the Th2-selective receptor chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) also 1) express high levels of CXCR5, and 2) display a transitional CD45RA\/RO phenotype and consistently do not produce significant amounts of cytokines when immediately analyzed ex vivo. Hence, they represent precursors of Th2 effector cells, a conclusion confirmed by their robust production of IL-4, IL-5, and IL-13, but not IFN-\u03b3, after in vitro activation. CD4+ T cells, which express only intermediate levels of CXCR5, instead develop into IFN-\u03b3-producing cells under identical culture conditions, thus establishing a correlation between relative levels of CXCR5 expression and the acquired cytokine profile. Because CXCR5 is critically involved in follicular localization, the results suggest that these CRTH2+ Th2 cells preferentially develop their cytokine-producing phenotype within germinal centers (GCs), whereas extrafollicular differentiation instead promotes Th1 development. In support for this proposal, we show that T cells with an intermediate expression of CXCR5 can be forced to also produce IL-4 and IL-13 if cultured with allogenic GC B cells. Finally, we demonstrate that the previously described CD57+ GC T cells also express high levels of CXCR5 but instead of comprising a Th2 precursor, they represent anergized T cells. Taken together, these data suggest that GCs and B cells regulate CD4+ T cell differentiation in a finely tuned fashion, either by promoting differentiation of Th2 cells, which apparently leave the lymphoid tissue before evolving a cytokine-producing phenotype, or by furnishing T cell unresponsiveness.<\/jats:p>","DOI":"10.4049\/jimmunol.171.4.1657","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T19:42:39Z","timestamp":1398022959000},"page":"1657-1666","source":"Crossref","is-referenced-by-count":48,"title":["Germinal Centers Regulate Human Th2 Development"],"prefix":"10.1093","volume":"171","author":[{"given":"Bengt","family":"Johansson-Lindbom","sequence":"first","affiliation":[{"name":"Department of Immunotechnology, Lund University , Lund ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sigurdur","family":"Ingvarsson","sequence":"additional","affiliation":[{"name":"Department of Immunotechnology, Lund University , Lund ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl A K","family":"Borrebaeck","sequence":"additional","affiliation":[{"name":"Department of Immunotechnology, Lund University , Lund ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2003,8,15]]},"reference":[{"key":"2026020210191192200_R1","first-page":"561","volume-title":"Annu. 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