{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,15]],"date-time":"2026-11-15T06:22:43Z","timestamp":1794723763346,"version":"4.9.1"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,2,17]],"date-time":"2005-02-17T00:00:00Z","timestamp":1108598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2005,3]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Schistosomiasis mansoni, a tropical helminthic disease, is caused by disseminated worm eggs that induce CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell mediated granulomatous inflammation and fibrosis. T suppressor cell activity has been proposed as one of the mechanisms active in the down\u2010modulation of the murine disease during the chronic stage (16\u201320\u2003weeks of the infection). In recent years a new category of the CD4\n                    <jats:sup>+<\/jats:sup>\n                    \u2003CD25\n                    <jats:sup>+<\/jats:sup>\n                    T regulatory (Treg) lymphocyte has been identified that maintains immune tolerance to self, and also functions in the regulation of parasite\u2010induced immunopathology. The Foxp3 gene which encodes the transcription factor Scurfin was found to be expressed by and required for the generation of CD4\n                    <jats:sup>+<\/jats:sup>\n                    \u2003CD25\n                    <jats:sup>+<\/jats:sup>\n                    T reg. At 8\u2003weeks of the infection Foxp3 gene expression of splenocytes was similar to that of na\u00efve mice, but increased fourfold by 16\u2003weeks. In contrast, granulomatous livers at 8 and 16\u2003weeks showed 10\u2010 and 30\u2010fold increases, respectively, in gene expression compared with normal liver. The percentage of granuloma CD4\n                    <jats:sup>+<\/jats:sup>\n                    \u2003CD25\n                    <jats:sup>+<\/jats:sup>\n                    T cells rose from 12% at 8\u2003weeks to 88% at 16\u2003weeks of the infection. Foxp3 expression was 3\u00b75\u2010fold higher in the CD4\n                    <jats:sup>+<\/jats:sup>\n                    \u2003CD25\n                    <jats:sup>+<\/jats:sup>\n                    versus the CD4\n                    <jats:sup>+<\/jats:sup>\n                    \u2003CD25\n                    <jats:sup>\u2013<\/jats:sup>\n                    T cells in the 8\u2003week infection granulomas. As a novel observation neuropilin\u20101 membrane expression, a recently identified marker for Treg, was correlated with Foxp3 expression in the granuloma CD4\n                    <jats:sup>+<\/jats:sup>\n                    \u2003CD25\n                    <jats:sup>+<\/jats:sup>\n                    but not the CD25\n                    <jats:sup>\u2013<\/jats:sup>\n                    cells. Co\u2010incubation with polyclonal stimulation of CD4\n                    <jats:sup>+<\/jats:sup>\n                    \u2003CD25\n                    <jats:sup>+<\/jats:sup>\n                    splenic cells with CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD25\n                    <jats:sup>\u2013<\/jats:sup>\n                    cells suppressed proliferation of the latter. Retroviral transfer of the Foxp3 gene at the onset of granuloma formation enhanced fourfold Foxp3 expression in the granuloma CD4\n                    <jats:sup>+<\/jats:sup>\n                    \u2003CD25\n                    <jats:sup>+<\/jats:sup>\n                    T cells and strongly suppressed full granuloma development. Gene transfer also significantly enhanced transforming growth factor\u2010\u03b2, interferon\u2010\u03b3 and interleukin\u20104 but not interleukin\u201010 expression. It is concluded, that CD4\n                    <jats:sup>+<\/jats:sup>\n                    \u2003CD25\n                    <jats:sup>+<\/jats:sup>\n                    , Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    Treg cells also regulate schistosome egg\u2010induced immunopathology.\n                  <\/jats:p>","DOI":"10.1111\/j.1365-2567.2004.02083.x","type":"journal-article","created":{"date-parts":[[2005,2,17]],"date-time":"2005-02-17T15:44:41Z","timestamp":1108655081000},"page":"410-417","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Retroviral Foxp3 gene transfer ameliorates liver granuloma pathology in\n                    <i>Schistosoma mansoni<\/i>\n                    infected mice"],"prefix":"10.1111","volume":"114","author":[{"given":"Kameshwar P.","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herve C.","family":"Gerard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan P.","family":"Hudson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thipparthi R.","family":"Reddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dov L.","family":"Boros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,2,17]]},"reference":[{"key":"e_1_2_21_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra012396"},{"key":"e_1_2_21_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(99)80090-2"},{"key":"e_1_2_21_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.114.5.1437"},{"key":"e_1_2_21_5_2","doi-asserted-by":"crossref","first-page":":2150","DOI":"10.4049\/jimmunol.115.1.150","article-title":"Immune responses to a soluble schistosomal egg antigen preparation during chronic primary infection with Schistosoma mansoni","volume":"115","author":"Colley DG","year":"1975","journal-title":"J Immunol"},{"key":"e_1_2_21_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.143.3.696"},{"key":"e_1_2_21_7_2","doi-asserted-by":"crossref","first-page":"363","DOI":"10.4049\/jimmunol.127.1.363","article-title":"Modulation of granulomatous hypersensitivity II. 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