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dc.contributor.authorFALLON, PADRAIC
dc.date.accessioned2009-09-17T17:15:12Z
dc.date.available2009-09-17T17:15:12Z
dc.date.issued2004
dc.date.submitted2004en
dc.identifier.citationSmith, P., Walsh, C.M, Mangan, N.E., Fallon, R.E., Sayers, J.R., McKenzie, A.N. and Fallon, P.G., `Schistosoma mansoni worms induce anergy of T cells via selective up-regulation of programmed death ligand 1 on macrophages? in Journal of Immunology, 173, (2), 2004, pp 1240 - 1248en
dc.identifier.otherYen
dc.identifier.otherY
dc.identifier.urihttp://hdl.handle.net/2262/32916
dc.descriptionPUBLISHEDen
dc.description.abstractInfectious 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) via an IL-4-, IL-13-, IL-10-, TGF--, and NO-independent, but cell contact-dependent, mechanism. F4/80+ M isolated from worm-infected mice were shown to induce anergy of naive T cells in vitro. Furthermore, naive M exposed to live worms in vitro also induced anergy in naive T cells. Flow cytometry on in vivo and in vitro worm-modulated M 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 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.en
dc.format.extent329613 bytes
dc.format.extent1240en
dc.format.extent1248en
dc.format.mimetypeapplication/pdf
dc.language.isoenen
dc.publisherThe Journal of Immunologyen
dc.relation.ispartofseriesJournal of Immunologyen
dc.relation.ispartofseries173en
dc.relation.ispartofseries2en
dc.rightsYen
dc.subjectClinical Medicineen
dc.titleSchistosoma mansoni worms induce anergy of T cells via selective up-regulation of programmed death ligand 1 on macrophagesen
dc.typeJournal Articleen
dc.contributor.sponsorScience Foundation Ireland
dc.contributor.sponsorIrish Research Council for Science Engineering and Technologyen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/pfallon
dc.identifier.rssinternalid25370


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