{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:28:46Z","timestamp":1791404926868,"version":"4.3.3"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2007,10,1]],"date-time":"2007-10-01T00:00:00Z","timestamp":1191196800000},"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":[[2007,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The T cell coinhibitory receptor CTLA-4 has been implicated in the down-regulation of T cell function that is a quintessential feature of chronic human filarial infections. In a laboratory model of filariasis, Litomosoides sigmodontis infection of susceptible BALB\/c mice, we have previously shown that susceptibility is linked both to a CD4+CD25+ regulatory T (Treg) cell response, and to the development of hyporesponsive CD4+ T cells at the infection site, the pleural cavity. We now provide evidence that L. sigmodontis infection drives the proliferation and activation of CD4+Foxp3+ Treg cells in vivo, demonstrated by increased uptake of BrdU and increased expression of CTLA-4, Foxp3, GITR, and CD25 compared with naive controls. The greatest increases in CTLA-4 expression were, however, seen in the CD4+Foxp3\u2212 effector T cell population which contained 78% of all CD4+CTLA-4+ cells in the pleural cavity. Depletion of CD25+ cells from the pleural CD4+ T cell population did not increase their Ag-specific proliferative response in vitro, suggesting that their hyporesponsive phenotype is not directly mediated by CD4+CD25+ Treg cells. Once infection had established, killing of adult parasites could be enhanced by neutralization of CTLA-4 in vivo, but only if performed in combination with the depletion of CD25+ Treg cells. This work suggests that during filarial infection CTLA-4 coinhibition and CD4+CD25+ Treg cells form complementary components of immune regulation that inhibit protective immunity in vivo.<\/jats:p>","DOI":"10.4049\/jimmunol.179.7.4626","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T18:54:06Z","timestamp":1397847246000},"page":"4626-4634","source":"Crossref","is-referenced-by-count":101,"title":["CTLA-4 and CD4+CD25+ Regulatory T Cells Inhibit Protective Immunity to Filarial Parasites In Vivo"],"prefix":"10.1093","volume":"179","author":[{"given":"Matthew D","family":"Taylor","sequence":"first","affiliation":[{"name":"Institute of Immunology and Infection Research, University of Edinburgh ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjanette","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon A","family":"Babayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odile","family":"Bain","sequence":"additional","affiliation":[{"name":"Parasitologie Compare\u0301e et Mode\u0300les Expe\u0301rimentaux, Muse\u0301um National d\u2019Histoire Naturelle , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Culshaw","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":"286","published-online":{"date-parts":[[2007,10,1]]},"reference":[{"key":"2026012810575093300_R1","first-page":"413","volume-title":"Immunology","year":"1977"},{"key":"2026012810575093300_R2","first-page":"172","volume-title":"J. 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