{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T07:03:21Z","timestamp":1788851001989,"version":"build-2803163510"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,8,6]]},"abstract":"\n Background<\/jats:title>\n \n Inflammation underlies many forms of pulmonary hypertension (\n PH<\/jats:styled-content>\n ), including that resulting from\n Schistosoma<\/jats:italic>\n infection, a major cause of\n PH<\/jats:styled-content>\n worldwide. Schistosomiasis\u2010associated\n PH<\/jats:styled-content>\n is proximately triggered by embolization of parasite eggs into the lungs, resulting in localized type 2 inflammation. However, the role of\n CD<\/jats:styled-content>\n 4\n +<\/jats:sup>\n T cells in this disease is not well defined.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We used a mouse model of schistosomiasis\u2010associated\n PH<\/jats:styled-content>\n , induced by intraperitoneal egg sensitization followed by intravenous egg challenge, with outcomes including right ventricle systolic pressure measured by cardiac catheterization, and cell density and phenotype assessed by flow cytometry. We identified that embolization of\n Schistosoma<\/jats:italic>\n eggs into lungs of egg\u2010sensitized mice increased the perivascular density of T\u2010helper 2 (Th2)\n CD<\/jats:styled-content>\n 4\n +<\/jats:sup>\n T cells by recruitment of cells from the circulation and triggered type 2 inflammation. Parabiosis confirmed that egg embolization is required for localized type 2 immunity. We found Th2\n CD<\/jats:styled-content>\n 4\n +<\/jats:sup>\n T cells were necessary for\n Schistosoma<\/jats:italic>\n \u2010induced\n PH<\/jats:styled-content>\n , given that deletion of\n CD<\/jats:styled-content>\n 4\n +<\/jats:sup>\n T cells or inhibiting their Th2 function protected against type 2 inflammation and\n PH<\/jats:styled-content>\n following\n Schistosoma<\/jats:italic>\n exposure. We also observed that adoptive transfer of\n Schistosoma<\/jats:italic>\n \u2010sensitized\n CD<\/jats:styled-content>\n 4\n +<\/jats:sup>\n Th2 cells was sufficient to drive type 2 inflammation and\n PH<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Th2\n CD<\/jats:styled-content>\n 4\n +<\/jats:sup>\n T cells are a necessary and sufficient component for the type 2 inflammation\u2010induced\n PH<\/jats:styled-content>\n following\n Schistosoma<\/jats:italic>\n exposure.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.119.013111","type":"journal-article","created":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T10:56:06Z","timestamp":1563965766000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":38,"title":["Th2 CD4\n +<\/sup>\n T Cells Are Necessary and Sufficient for\n Schistosoma\u2010<\/i>\n Pulmonary Hypertension"],"prefix":"10.1161","volume":"8","author":[{"given":"Rahul","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Medicine University of Colorado Anschutz Medical Campus Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Mickael","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Colorado Anschutz Medical Campus Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biruk","family":"Kassa","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Colorado Anschutz Medical Campus Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Sanders","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Colorado Anschutz Medical Campus Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Koyanagi","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Colorado Anschutz Medical Campus Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Hernandez\u2010Saavedra","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Colorado Anschutz Medical Campus Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Freeman","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Colorado Anschutz Medical Campus Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Morales\u2010Cano","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology School of Medicine University Complutense of Madrid Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM) Madrid Spain"},{"name":"Ciber Enfermedades Respiratorias (CIBERES) Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Cogolludo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology School of Medicine University Complutense of Madrid Instituto de Investigaci\u00f3n Sanitaria Gregorio Mara\u00f1\u00f3n (IiSGM) Madrid Spain"},{"name":"Ciber Enfermedades Respiratorias (CIBERES) Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy S.","family":"McKee","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Colorado Anschutz Medical Campus Aurora CO"},{"name":"Department of Microbiology and Immunology University of Colorado Anschutz Medical Campus Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Fontenot","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Colorado Anschutz Medical Campus Aurora CO"},{"name":"Department of Microbiology and Immunology University of Colorado Anschutz Medical Campus Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghazwan","family":"Butrous","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences University of Kent Canterbury United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rubin M.","family":"Tuder","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Colorado Anschutz Medical Campus Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian B.","family":"Graham","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Colorado Anschutz Medical Campus Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201202-0335OC"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01214-2017"},{"key":"e_1_3_2_4_2","unstructured":"Schistosomiasis: World Health Organization Fact sheet No 115. Updated March 2013. Available at: http:\/\/www.who.int\/mediacentre\/factsheets\/fs115\/en\/index.html. Accessed January 15 2018."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.4103\/0974-6013.85614"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0000000000000300"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.10-0048"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020903"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201410-1820OC"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.162.2.920"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.100063"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15494"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.003072"},{"key":"e_1_3_2_14_2","first-page":"50556","article-title":"Parabiosis in mice: a detailed protocol","volume":"80","author":"Kamran P","year":"2013","unstructured":"Kamran P, Sereti KI, Zhao P, Ali SR, Weissman IL, Ardehali R. Parabiosis in mice: a detailed protocol. J Vis Exp. 2013;80:50556.","journal-title":"J Vis Exp"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2818.1997.2070765.x"},{"key":"e_1_3_2_16_2","first-page":"328","article-title":"Conditions affecting the accuracy of potassium hydroxide digestion techniques for counting Schistosoma mansoni eggs in tissues","volume":"39","author":"Cheever AW","year":"1968","unstructured":"Cheever AW. Conditions affecting the accuracy of potassium hydroxide digestion techniques for counting Schistosoma mansoni eggs in tissues. Bull World Health Organ. 1968;39:328\u2013331.","journal-title":"Bull World Health Organ"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2013.08.004"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20130091"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90030-G"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.5.1551"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3083.1998.00376.x"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-14-282"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200903-0355OC"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.312058"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071008"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1424774112"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00531.2016"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20171767"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23303"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001724"},{"key":"e_1_3_2_31_2","first-page":"63","article-title":"Primary immunodeficiency state in a child with the pulmonary hypertension syndrome","volume":"47","author":"Bo\u01d0kova NV","year":"1985","unstructured":"Bo\u01d0kova NV. [Primary immunodeficiency state in a child with the pulmonary hypertension syndrome]. [Article in Russian]. Arkh Patol. 1985;47:63\u201366.","journal-title":"Arkh Patol"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2014.00077"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.162.6.3256"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-04-015933"},{"issue":"193","key":"e_1_3_2_35_2","first-page":"3590","article-title":"T cell\u2010derived IL\u20104\/IL\u201013 protects mice against fatal Schistosoma mansoni infection independently of basophils","volume":"2014","author":"Schwartz C","year":"1950","unstructured":"Schwartz C, Oeser K, Prazeres da Costa C, Layland LE, Voehringer D. T cell\u2010derived IL\u20104\/IL\u201013 protects mice against fatal Schistosoma mansoni infection independently of basophils. J Immunol. 1950;2014(193):3590\u20133599.","journal-title":"J Immunol"},{"issue":"192","key":"e_1_3_2_36_2","first-page":"2965","article-title":"Cutting edge: control of Mycobacterium tuberculosis infection by a subset of lung parenchyma\u2010homing CD4 T cells","volume":"2014","author":"Sakai S","year":"1950","unstructured":"Sakai S, Kauffman KD, Schenkel JM, McBerry CC, Mayer\u2010Barber KD, Masopust D, Barber DL. Cutting edge: control of Mycobacterium tuberculosis infection by a subset of lung parenchyma\u2010homing CD4 T cells. J Immunol. 1950;2014(192):2965\u20132969.","journal-title":"J Immunol"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2017.60"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0006613"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005867"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.119.013111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:53:09Z","timestamp":1715601189000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.119.013111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,6]]},"references-count":38,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2019,8,6]]}},"alternative-id":["10.1161\/JAHA.119.013111"],"URL":"https:\/\/doi.org\/10.1161\/jaha.119.013111","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,6]]},"assertion":[{"value":"2019-04-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e013111"}}