{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:29:06Z","timestamp":1791404946884,"version":"4.3.3"},"reference-count":76,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2005,4,1]],"date-time":"2005-04-01T00:00:00Z","timestamp":1112313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Human filarial parasites cause chronic infection associated with long-term down-regulation of the host\u2019s immune response. We show here that CD4+ T cell regulation is the main determinant of parasite survival. In a laboratory model of infection, using Litomosoides sigmodontis in BALB\/c mice, parasites establish for &amp;gt;60 days in the thoracic cavity. During infection, CD4+ T cells at this site express increasing levels of CD25, CTLA-4, and glucocorticoid-induced TNF receptor family-related gene (GITR), and by day 60, up to 70% are CTLA-4+GITRhigh, with a lesser fraction coexpressing CD25. Upon Ag stimulation, CD4+CTLA-4+GITRhigh cells are hyporesponsive for proliferation and cytokine production. To test the hypothesis that regulatory T cell activity maintains hyporesponsiveness and prolongs infection, we treated mice with Abs to CD25 and GITR. Combined Ab treatment was able to overcome an established infection, resulting in a 73% reduction in parasite numbers (p &amp;lt; 0.01). Parasite killing was accompanied by increased Ag-specific immune responses and markedly reduced levels of CTLA-4 expression. The action of the CD25+GITR+ cells was IL-10 independent as in vivo neutralization of IL-10R did not restore the ability of the immune system to kill parasites. These data suggest that regulatory T cells act, in an IL-10-independent manner, to suppress host immunity to filariasis.<\/jats:p>","DOI":"10.4049\/jimmunol.174.8.4924","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T22:25:14Z","timestamp":1398032714000},"page":"4924-4933","source":"Crossref","is-referenced-by-count":236,"title":["Removal of Regulatory T Cell Activity Reverses Hyporesponsiveness and Leads to Filarial Parasite Clearance In Vivo"],"prefix":"10.1093","volume":"174","author":[{"given":"Matthew D","family":"Taylor","sequence":"first","affiliation":[{"name":"Institute of Immunology and Infection Research, University of Edinburgh , Edinburgh ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"LeGoff","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research, University of Edinburgh , Edinburgh ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjanette","family":"Harris","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research, University of Edinburgh , Edinburgh ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Malone","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research, University of Edinburgh , Edinburgh ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith E","family":"Allen","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research, University of Edinburgh , Edinburgh ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick M","family":"Maizels","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research, University of Edinburgh , Edinburgh ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2005,4,15]]},"reference":[{"key":"2026020212244726700_R1","first-page":"413","volume-title":"Immunology","year":"1977"},{"key":"2026020212244726700_R2","first-page":"172","volume-title":"J. 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