{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:34:40Z","timestamp":1791401680786,"version":"4.3.3"},"reference-count":64,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,1,3]]},"abstract":"<jats:p>T cell homing to peripheral lymph nodes (PLNs) is defined by a multistep sequence of interactions between lymphocytes and endothelial cells in high endothelial venules (HEVs). After initial tethering and rolling via L-selectin, firm adhesion of T cells requires rapid upregulation of lymphocyte function\u2013associated antigen 1 (LFA-1) adhesiveness by a previously unknown pathway that activates a G\u03b1i-linked receptor. Here, we used intravital microscopy of murine PLNs to study the role of thymus-derived chemotactic agent (TCA)-4 (secondary lymphoid tissue chemokine, 6Ckine, Exodus-2) in homing of adoptively transferred T cells from T-GFP mice, a transgenic strain that expresses green fluorescent protein (GFP) selectively in naive T lymphocytes (TGFP cells). TCA-4 was constitutively presented on the luminal surface of HEVs, where it was required for LFA-1 activation on rolling TGFP cells. Desensitization of the TCA-4 receptor, CC chemokine receptor 7 (CCR7), blocked TGFP cell adherence in wild-type HEVs, whereas desensitization to stromal cell\u2013derived factor (SDF)-1\u03b1 (the ligand for CXC chemokine receptor 4 [CXCR4]) did not affect TGFP cell behavior. TCA-4 protein was not detected on the luminal surface of PLN HEVs in plt\/plt mice, which have a congenital defect in T cell homing to PLNs. Accordingly, TGFP cells rolled but did not arrest in plt\/plt HEVs. When TCA-4 was injected intracutaneously into plt\/plt mice, the chemokine entered afferent lymph vessels and accumulated in draining PLNs. 2 h after intracutaneous injection, luminal presentation of TCA-4 was detectable in a subset of HEVs, and LFA-1\u2013mediated TGFP cell adhesion was restored in these vessels. We conclude that TCA-4 is both required and sufficient for LFA-1 activation on rolling T cells in PLN HEVs. This study also highlights a hitherto undocumented role for chemokines contained in afferent lymph, which may modulate leukocyte recruitment in draining PLNs.<\/jats:p>","DOI":"10.1084\/jem.191.1.61","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"61-76","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":336,"title":["The Cc Chemokine Thymus-Derived Chemotactic Agent 4 (Tca-4, Secondary Lymphoid Tissue Chemokine, 6ckine, Exodus-2) Triggers Lymphocyte Function\u2013Associated Antigen 1\u2013Mediated Arrest of Rolling T Lymphocytes in Peripheral Lymph Node High Endothelial Venules"],"prefix":"10.1084","volume":"191","author":[{"given":"Jens V.","family":"Stein","sequence":"first","affiliation":[{"name":"aThe Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antal","family":"Rot","sequence":"additional","affiliation":[{"name":"dNovartis Forschungsinstitut, A-1235 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Luo","sequence":"additional","affiliation":[{"name":"bDepartment of Pathology, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjunath","family":"Narasimhaswamy","sequence":"additional","affiliation":[{"name":"aThe Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Nakano","sequence":"additional","affiliation":[{"name":"eDepartment of Immunology, Toho University School of Medicine, Tokyo 143-8540, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Gunn","sequence":"additional","affiliation":[{"name":"fDivision of Cardiology, Duke University Medical Center, Durham, North Carolina 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Matsuzawa","sequence":"additional","affiliation":[{"name":"gInstitute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Quackenbush","sequence":"additional","affiliation":[{"name":"aThe Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115"},{"name":"cChildren's Hospital, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin E.","family":"Dorf","sequence":"additional","affiliation":[{"name":"bDepartment of Pathology, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich H.","family":"von Andrian","sequence":"additional","affiliation":[{"name":"aThe Center for Blood Research, Harvard Medical School, Boston, Massachusetts 02115"},{"name":"bDepartment of Pathology, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2000,1,3]]},"reference":[{"key":"2023072509131451800_R1","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1098\/rspb.1964.0001","article-title":"The route of re-circulation of lymphocytes in the rat","volume":"159","author":"Gowans","year":"1964","journal-title":"Proc. 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