{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:40:32Z","timestamp":1791276032754,"version":"4.1.0"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2004,7,1]],"date-time":"2004-07-01T00:00:00Z","timestamp":1088640000000},"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":[[2004,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Infectious pathogens can selectively stimulate activation or suppression of T cells to facilitate their survival within humans. In this study we demonstrate that the trematode parasite Schistosoma mansoni has evolved with two distinct mechanisms to suppress T cell activation. During the initial 4- to 12-wk acute stages of a worm infection both CD4+ and CD8+ T cells are anergized. In contrast, infection with male and female worms induced T cell anergy at 4 wk, which was replaced after egg laying by T cell suppression via a known NO-dependent mechanism, that was detected for up to 40 wk after infection. Worm-induced anergy was mediated by splenic F4\/80+ macrophages (M\u03c6) via an IL-4-, IL-13-, IL-10-, TGF-\u03b2-, and NO-independent, but cell contact-dependent, mechanism. F4\/80+ M\u03c6 isolated from worm-infected mice were shown to induce anergy of naive T cells in vitro. Furthermore, naive M\u03c6 exposed to live worms in vitro also induced anergy in naive T cells. Flow cytometry on in vivo and in vitro worm-modulated M\u03c6 revealed that of the family of B7 costimulatory molecules, only programmed death ligand 1 (PD-L1) was selectively up-regulated. The addition of inhibitory mAb against PD-L1, but not PD-L2, to worm-modulated M\u03c6 completely blocked the ability of these cells to anergize T cells. These data highlight a novel mechanism through which S. mansoni worms have usurped the natural function of PD-L1 to reduce T cell activation during early acute stages of infection before the subsequent emergence of egg-induced T cell suppression in the chronic stages of infection.<\/jats:p>","DOI":"10.4049\/jimmunol.173.2.1240","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T19:37:22Z","timestamp":1398022642000},"page":"1240-1248","source":"Crossref","is-referenced-by-count":164,"title":["<i>Schistosoma mansoni<\/i>\n                    Worms Induce Anergy of T Cells via Selective Up-Regulation of Programmed Death Ligand 1 on Macrophages"],"prefix":"10.1093","volume":"173","author":[{"given":"Philip","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Trinity College , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitriona M","family":"Walsh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Trinity College , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niamh E","family":"Mangan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Trinity College , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosie E","family":"Fallon","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Trinity College , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon R","family":"Sayers","sequence":"additional","affiliation":[{"name":"Division of Genomic Medicine, University of Sheffield Medical School , Sheffield ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew N J","family":"McKenzie","sequence":"additional","affiliation":[{"name":"Medical Research Council, Laboratory of Molecular Biology , Cambridge ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padraic G","family":"Fallon","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Trinity College , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,7,15]]},"reference":[{"key":"2026020212075735100_R1","first-page":"499","volume-title":"Nat. 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