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Using a permissive murine model of filariasis, <jats:italic>Litomosoides sigmodontis<\/jats:italic> infection of inbred mice, we demonstrate rapid recruitment and increased <jats:italic>in vivo<\/jats:italic> proliferation of CD4<jats:sup>+<\/jats:sup>Foxp3<jats:sup>+<\/jats:sup> Treg cells upon exposure to infective L3 larvae. Within 7 days post\u2010infection this resulted in an increased percentage of CD4<jats:sup>+<\/jats:sup>T cells at the infection site expressing Foxp3. Antibody\u2010mediated depletion of CD25<jats:sup>+<\/jats:sup> cells prior to infection to remove pre\u2010existing \u2018natural\u2019 CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>Foxp3<jats:sup>+<\/jats:sup> Treg cells, while not affecting initial larval establishment, significantly reduced the number of adult parasites recovered 60 days post\u2010infection. Anti\u2010CD25 pre\u2010treatment also impaired the fecundity of the surviving female parasites, which had reduced numbers of healthy eggs and microfilaria within their uteri, translating to a reduced level of blood microfilaraemia. Enhanced parasite killing was associated with augmented <jats:italic>in vitro<\/jats:italic> production of antigen\u2010specific IL\u20104, IL\u20105, IL\u201013 and IL\u201010. Thus, upon infection filarial larvae rapidly provoke a CD4<jats:sup>+<\/jats:sup>Foxp3<jats:sup>+<\/jats:sup> Treg\u2010cell response, biasing the initial CD4<jats:sup>+<\/jats:sup> T\u2010cell response towards a regulatory phenotype. These CD4<jats:sup>+<\/jats:sup>Foxp3<jats:sup>+<\/jats:sup> Treg cells are predominantly recruited from the \u2018natural\u2019 regulatory pool and act to inhibit protective immunity over the full course of infection.<\/jats:p>","DOI":"10.1002\/eji.200838727","type":"journal-article","created":{"date-parts":[[2008,12,17]],"date-time":"2008-12-17T21:39:41Z","timestamp":1229549981000},"page":"192-206","source":"Crossref","is-referenced-by-count":112,"title":["Early recruitment of natural CD4<sup>+<\/sup>Foxp3<sup>+<\/sup> Treg cells by infective larvae determines the outcome of filarial infection"],"prefix":"10.1002","volume":"39","author":[{"given":"Matthew D.","family":"Taylor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nienke","family":"van der Werf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjanette","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea L.","family":"Graham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odile","family":"Bain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith E.","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick M.","family":"Maizels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,5]]},"reference":[{"key":"e_1_2_7_2_2","first-page":"413","article-title":"Specific cellular immune unresponsiveness in human filariasis","volume":"33","author":"Ottesen E. 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