{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:34:52Z","timestamp":1791401692631,"version":"4.3.3"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2001,1,1]],"date-time":"2001-01-01T00:00:00Z","timestamp":978307200000},"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":[[2001,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>CCR4, a chemokine receptor for macrophage-derived chemokine (MDC) and thymus and activation-regulated chemokine (TARC), has been implicated as a preferential marker for Th2 lymphocytes. Following in vitro polarization protocols, most Th2 lymphocytes express CCR4 and respond to its ligands TARC and MDC, whereas Th1 lymphocytes express CXC chemokine receptor 3 and CCR5 (but not CCR4). We show in this study that CCR4 is a major receptor for MDC and TARC on T lymphocytes, as anti-CCR4 mAbs significantly inhibit the migration of these cells to MDC and TARC. CCR4 is also highly expressed in most single-positive CD4+ thymocytes and on a major fraction of blood nonintestinal (\u03b14\u03b27\u2212) memory CD4 lymphocytes, including almost all skin memory CD4+ cells expressing the cutaneous lymphocyte Ag (CLA), but weakly or not expressed in other subsets in thymus and blood. Interestingly, major fractions of circulating CCR4+ memory CD4 lymphocytes coexpress the Th1-associated receptors CXC chemokine receptor 3 and CCR5, suggesting a potential problem in using these markers for Th1 vs Th2 lymphocyte cells. Moreover, although production of Th2 cytokines in blood T cells is associated with CCR4+ CD4 lymphocytes, significant numbers of freshly isolated circulating CCR4+ memory CD4 lymphocytes (including both CLA+ and CLA\u2212 fractions) readily express the Th1 cytokine IFN-\u03b3 after short-term stimulation. Our results are consistent with a role for CCR4 as a major trafficking receptor for systemic memory T cells, and indicate that the patterns and regulation of chemokine receptor expression in vivo are more complex than indicated by current in vitro models of Th1 vs Th2 cell generation.<\/jats:p>","DOI":"10.4049\/jimmunol.166.1.103","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T01:32:59Z","timestamp":1398043979000},"page":"103-111","source":"Crossref","is-referenced-by-count":164,"title":["C-C Chemokine Receptor 4 Expression Defines a Major Subset of Circulating Nonintestinal Memory T Cells of Both Th1 and Th2 Potential"],"prefix":"10.1093","volume":"166","author":[{"given":"David P","family":"Andrew","sequence":"first","affiliation":[{"name":"Millennium Pharmaceuticals , Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Ruffing","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals , Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang H","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine , Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Miao","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals , Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Heath","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals , Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Li","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals , Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine","family":"Murphy","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals , Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J","family":"Campbell","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine , Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene C","family":"Butcher","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine , Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Wu","sequence":"additional","affiliation":[{"name":"Millennium Pharmaceuticals , Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2001,1,1]]},"reference":[{"key":"2025032713370508300_R1","first-page":"229","volume-title":"Ther. 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