{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:14:11Z","timestamp":1793297651164,"version":"4.5.0"},"reference-count":72,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2016,5,13]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>CD4 T cells are involved in the pathogenesis of atherosclerosis, but atherosclerosis-specific CD4 T cells have not been described. Moreover, the chemokine(s) that regulates T-cell trafficking to the atherosclerotic lesions is also unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              In\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice with mature atherosclerotic lesions (5 months of high fat diet), we find that most aortic T cells express CCR5 and interferon-\u03b3 with a unique combination of cell surface markers (CD4\n              <jats:sup>+<\/jats:sup>\n              CD25\n              <jats:sup>\u2212<\/jats:sup>\n              CD44\n              <jats:sup>hi<\/jats:sup>\n              CD62L\n              <jats:sup>lo<\/jats:sup>\n              ) and transcription factors (FoxP3\n              <jats:sup>+<\/jats:sup>\n              T-bet\n              <jats:sup>+<\/jats:sup>\n              ). We call these cells CCR5Teff. We investigated the role of CCR5 in regulating T-cell homing to the atherosclerotic aorta and the functionality of the CCR5Teff cells.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              CCR5Teff cells are exclusively found in the aorta and para-aortic lymph nodes of\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice. They do not suppress T-cell proliferation in vitro and are less potent than regulatory T cells at inhibiting cytokine secretion. Blocking or knocking out CCR5 or its ligand CCL5 significantly blocks T-cell homing to atherosclerotic aortas. Transcriptomic analysis shows that CCR5Teff cells are more similar to effector T cells than to regulatory T cells. They secrete interferon-\u03b3, interleukin-2, interleukin-10, and tumor necrosis factor. Adoptive transfer of these CCR5Teff cells significantly increases atherosclerosis.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              CCR5 is specifically needed for CD4 T-cell homing to the atherosclerotic plaques. CCR5\n              <jats:sup>+<\/jats:sup>\n              CD4 T cells express an unusual combination of transcription factors, FoxP3 and T-bet. Although CCR5Teff express FoxP3, we showed that they are not regulatory and adoptive transfer of these cells exacerbates atherosclerosis.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.116.308648","type":"journal-article","created":{"date-parts":[[2016,3,29]],"date-time":"2016-03-29T02:49:05Z","timestamp":1459219745000},"page":"1540-1552","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":133,"title":["CCR5\n            <sup>+<\/sup>\n            T-bet\n            <sup>+<\/sup>\n            FoxP3\n            <sup>+<\/sup>\n            Effector CD4 T Cells Drive Atherosclerosis"],"prefix":"10.1161","volume":"118","author":[{"given":"Jie","family":"Li","sequence":"first","affiliation":[{"name":"From the Division of Inflammation Biology (J.L., S.M., T.K., D.W., T.G., J.M., K.L.) and Bioinformatics Core (A.G.), La Jolla Institute for Allergy &amp; Immunology, CA; Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany (C.W.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (C.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"McArdle","sequence":"additional","affiliation":[{"name":"From the Division of Inflammation Biology (J.L., S.M., T.K., D.W., T.G., J.M., K.L.) and Bioinformatics Core (A.G.), La Jolla Institute for Allergy &amp; Immunology, CA; Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany (C.W.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (C.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amin","family":"Gholami","sequence":"additional","affiliation":[{"name":"From the Division of Inflammation Biology (J.L., S.M., T.K., D.W., T.G., J.M., K.L.) and Bioinformatics Core (A.G.), La Jolla Institute for Allergy &amp; Immunology, CA; Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany (C.W.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (C.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Kimura","sequence":"additional","affiliation":[{"name":"From the Division of Inflammation Biology (J.L., S.M., T.K., D.W., T.G., J.M., K.L.) and Bioinformatics Core (A.G.), La Jolla Institute for Allergy &amp; Immunology, CA; Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany (C.W.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (C.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Wolf","sequence":"additional","affiliation":[{"name":"From the Division of Inflammation Biology (J.L., S.M., T.K., D.W., T.G., J.M., K.L.) and Bioinformatics Core (A.G.), La Jolla Institute for Allergy &amp; Immunology, CA; Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany (C.W.); 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and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (C.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Weber","sequence":"additional","affiliation":[{"name":"From the Division of Inflammation Biology (J.L., S.M., T.K., D.W., T.G., J.M., K.L.) and Bioinformatics Core (A.G.), La Jolla Institute for Allergy &amp; Immunology, CA; Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany (C.W.); and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (C.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Ley","sequence":"additional","affiliation":[{"name":"From the Division of Inflammation Biology (J.L., S.M., T.K., D.W., T.G., J.M., K.L.) and Bioinformatics Core (A.G.), La Jolla Institute for Allergy &amp; Immunology, CA; Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Munich, Germany (C.W.); 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