{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:50:51Z","timestamp":1790470251463,"version":"4.1.0"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"22","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2017,5,30]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Innate antigen-presenting cells and adaptive immune T cells have been implicated in the development of hypertension. However, the T-lymphocyte subsets involved in the pathophysiology of hypertension remain unclear. A small subset of innate-like T cells expressing the \u03b3\u03b4 T cell receptor (TCR) rather than the \u03b1\u03b2 TCR could play a role in the initiation of the immune response in hypertension. We aimed to determine whether angiotensin (Ang) II caused kinetic changes in \u03b3\u03b4 T cells; deficiency in \u03b3\u03b4 T cells blunted Ang II-induced hypertension, vascular injury, and T-cell activation; and \u03b3\u03b4 T cells are associated with human hypertension.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Male C57BL\/6 wild-type and\n                      <jats:italic>Tcr\u03b4<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice, which are devoid of \u03b3\u03b4 T cells, or wild-type mice injected IP with control isotype IgG or \u03b3\u03b4 T cell-depleting antibodies, were infused or not with Ang II for 3, 7, or 14 days. T-cell profiling was determined by flow cytometry, systolic blood pressure (SBP) by telemetry, and mesentery artery endothelial function by pressurized myography. TCR \u03b3 constant region gene expression levels and clinical data of a whole blood gene expression microarray study, including normotensive and hypertensive subjects, were used to demonstrate an association between \u03b3\u03b4 T cells and SBP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Seven- and 14-day Ang II infusion increased \u03b3\u03b4 T-cell numbers and activation in the spleen of wild-type mice (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.05). Fourteen days of Ang II infusion increased SBP (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.01) and decreased mesenteric artery endothelial function (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.01) in wild-type mice, both of which were abrogated in\n                      <jats:italic>Tcr\u03b4<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.01). Anti-TCR\u03b3\u03b4 antibody-induced \u03b3\u03b4 T-cell depletion blunted Ang II-induced SBP rise and endothelial dysfunction (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.05), compared with isotype antibody-treated Ang II-infused mice. Ang II-induced T-cell activation in the spleen and perivascular adipose tissue was blunted in\n                      <jats:italic>Tcr\u03b4<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.01). In humans, the association between SBP and \u03b3\u03b4 T cells was demonstrated by a multiple linear regression model integrating whole blood TCR \u03b3 constant region gene expression levels and age and sex (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      =0.12,\n                      <jats:italic>P<\/jats:italic>\n                      &lt;1\u00d710\n                      <jats:sup>-6<\/jats:sup>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\u03b3\u03b4 T cells mediate Ang II-induced SBP elevation, vascular injury, and T-cell activation in mice. \u03b3\u03b4 T cells might contribute to the development of hypertension in humans.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.116.027058","type":"journal-article","created":{"date-parts":[[2017,3,22]],"date-time":"2017-03-22T21:08:38Z","timestamp":1490216918000},"page":"2155-2162","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":175,"title":["\u03b3\u03b4 T Cells Mediate Angiotensin II-Induced Hypertension and Vascular Injury"],"prefix":"10.1161","volume":"135","author":[{"given":"Antoine","family":"Caillon","sequence":"first","affiliation":[{"name":"From Lady Davis Institute for Medical Research (A.C., M.O.R.M., J.C.F.-A., K.-G.H., T.B., S.O., P.P., E.L.S.), Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital (E.L.S.), McGill University, Montr\u00e9al, Qu\u00e9bec, Canada; and Universitaire Ziekenhuizen Leuven Gasthuisberg, University of Leuven, Belgium (P.R.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Oneeb Rehman","family":"Mian","sequence":"additional","affiliation":[{"name":"From Lady Davis Institute for Medical Research (A.C., M.O.R.M., J.C.F.-A., K.-G.H., T.B., S.O., P.P., E.L.S.), Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital (E.L.S.), McGill University, Montr\u00e9al, Qu\u00e9bec, Canada; and Universitaire Ziekenhuizen Leuven Gasthuisberg, University of Leuven, Belgium (P.R.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio C.","family":"Fraulob-Aquino","sequence":"additional","affiliation":[{"name":"From Lady Davis Institute for Medical Research (A.C., M.O.R.M., J.C.F.-A., K.-G.H., T.B., S.O., P.P., E.L.S.), Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital (E.L.S.), McGill University, Montr\u00e9al, Qu\u00e9bec, Canada; and Universitaire Ziekenhuizen Leuven Gasthuisberg, University of Leuven, Belgium (P.R.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ku-Geng","family":"Huo","sequence":"additional","affiliation":[{"name":"From Lady Davis Institute for Medical Research (A.C., M.O.R.M., J.C.F.-A., K.-G.H., T.B., S.O., P.P., E.L.S.), Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital (E.L.S.), McGill University, Montr\u00e9al, Qu\u00e9bec, Canada; and Universitaire Ziekenhuizen Leuven Gasthuisberg, University of Leuven, Belgium (P.R.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tlili","family":"Barhoumi","sequence":"additional","affiliation":[{"name":"From Lady Davis Institute for Medical Research (A.C., M.O.R.M., J.C.F.-A., K.-G.H., T.B., S.O., P.P., E.L.S.), Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital (E.L.S.), McGill University, Montr\u00e9al, Qu\u00e9bec, Canada; and Universitaire Ziekenhuizen Leuven Gasthuisberg, University of Leuven, Belgium (P.R.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofiane","family":"Ouerd","sequence":"additional","affiliation":[{"name":"From Lady Davis Institute for Medical Research (A.C., M.O.R.M., J.C.F.-A., K.-G.H., T.B., S.O., P.P., E.L.S.), Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital (E.L.S.), McGill University, Montr\u00e9al, Qu\u00e9bec, Canada; and Universitaire Ziekenhuizen Leuven Gasthuisberg, University of Leuven, Belgium (P.R.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Sinnaeve","sequence":"additional","affiliation":[{"name":"From Lady Davis Institute for Medical Research (A.C., M.O.R.M., J.C.F.-A., K.-G.H., T.B., S.O., P.P., E.L.S.), Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital (E.L.S.), McGill University, Montr\u00e9al, Qu\u00e9bec, Canada; and Universitaire Ziekenhuizen Leuven Gasthuisberg, University of Leuven, Belgium (P.R.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Paradis","sequence":"additional","affiliation":[{"name":"From Lady Davis Institute for Medical Research (A.C., M.O.R.M., J.C.F.-A., K.-G.H., T.B., S.O., P.P., E.L.S.), Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital (E.L.S.), McGill University, Montr\u00e9al, Qu\u00e9bec, Canada; and Universitaire Ziekenhuizen Leuven Gasthuisberg, University of Leuven, Belgium (P.R.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto L.","family":"Schiffrin","sequence":"additional","affiliation":[{"name":"From Lady Davis Institute for Medical Research (A.C., M.O.R.M., J.C.F.-A., K.-G.H., T.B., S.O., P.P., E.L.S.), Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital (E.L.S.), McGill University, Montr\u00e9al, Qu\u00e9bec, Canada; and Universitaire Ziekenhuizen Leuven Gasthuisberg, University of Leuven, Belgium (P.R.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61766-8"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.111.187021"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu119"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-013-0413-9"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000181743.28028.57"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01118.2006"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070657"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032713-120216"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3298"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.3RU0914-443R"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3384"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3109\/08830189509061737"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000000761"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007037"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.145094"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.308111"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-016-0628-7"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.00689"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/hpw102"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.116.027058","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T02:32:34Z","timestamp":1715567554000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.116.027058"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,30]]},"references-count":19,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2017,5,30]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.116.027058"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.116.027058","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,30]]},"assertion":[{"value":"2016-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-03-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-03-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}