{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:19:11Z","timestamp":1790173151521,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19AI110495"],"award-info":[{"award-number":["U19AI110495"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Although fibrotic disorders are frequently assumed to be linked to TH2 cells, quantitative tissue interrogation studies have rarely been performed to establish this link and certainly many fibrotic diseases do not fall within the type 2\/allergic disease spectrum. We have previously linked two human autoimmune fibrotic diseases, IgG4-related disease and systemic sclerosis, to the clonal expansion and lesional accumulation of CD4+CTLs. In both these diseases TH2 cell accumulation was found to be sparse. Fibrosing mediastinitis linked to Histoplasma capsulatum infection histologically resembles IgG4-related disease in terms of the inflammatory infiltrate and fibrosis, and it provides an example of a fibrotic disease of infectious origin in which the potentially profibrotic T cells may be induced and reactivated by fungal Ags. We show in this study that, in this human disease, CD4+CTLs accumulate in the blood, are clonally expanded, infiltrate into disease lesions, and can be reactivated in vitro by H. capsulatum Ags. TH2 cells are relatively sparse at lesional sites. These studies support a general role for CD4+CTLs in inflammatory fibrosis and suggest that fibrosing mediastinitis is an Ag-driven disease that may provide important mechanistic insights into the pathogenesis of idiopathic fibrotic diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.2000433","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T22:17:32Z","timestamp":1608157052000},"page":"524-530","source":"Crossref","is-referenced-by-count":23,"title":["CD4+CTLs in Fibrosing Mediastinitis Linked to <i>Histoplasma capsulatum<\/i>"],"prefix":"10.1093","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7850-2658","authenticated-orcid":false,"given":"Hugues","family":"Allard-Chamard","sequence":"first","affiliation":[{"name":"Ragon Institute of MGH, MIT and Harvard , Cambridge, MA 02139"},{"name":"Division de Rhumatologie, Facult\u00e9 de M\u00e9decine et des Sciences de la Sant\u00e9 de l\u2019Universit\u00e9 de Sherbrooke et Centre de Recherche Clinique \u00c9tienne-Le Bel , Sherbrooke, Qu\u00e9bec J1K 2R1 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal","family":"Alsufyani","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT and Harvard , Cambridge, MA 02139"},{"name":"King Fahad Specialist Hospital , Dammam 32253 ,","place":["Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT and Harvard , Cambridge, MA 02139"},{"name":"Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University , Fukuoka 814-0133 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Xing","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT and Harvard , Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0812-4353","authenticated-orcid":false,"given":"Cory","family":"Perugino","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT and Harvard , Cambridge, MA 02139"},{"name":"Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital , Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0814-2989","authenticated-orcid":false,"given":"Vinay S","family":"Mahajan","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT and Harvard , Cambridge, MA 02139"},{"name":"Division of Pathology, Brigham and Women\u2019s Hospital , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph L","family":"Wheat","sequence":"additional","affiliation":[{"name":"MiraVista Diagnostics , Indianapolis, IN 46241"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"George S","family":"Deepe","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, University of Cincinnati College of Medicine , Cincinnati, OH 45267"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Loyd","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vanderbilt University Medical Center , Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiv","family":"Pillai","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT and Harvard , Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,2,1]]},"reference":[{"key":"2025022610330862100_r1","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1164\/rccm.201505-0964LE","article-title":"Further progress in understanding fibrosing mediastinitis","volume":"192","author":"Strock","year":"2015","journal-title":"Am. 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