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Thereby not only helminth\u2010specific but also nonhelminth\u2010specific bystander immune responses are suppressed. Here, we use the murine model of <jats:italic>Litomosoides sigmodontis<\/jats:italic> infection to elucidate the underlying mechanisms leading to this bystander T\u2010cell suppression. When OT\u2010II T cells specific for the third\u2010party antigen ovalbumin are transferred into helminth\u2010infected mice, these cells respond to antigen\u2010specific stimulation with reduced proliferation compared to activation within non\u2010infected mice. Thus, the presence of parasitic worms in the thoracic cavity translates to suppression of T cells with a different specificity at a different site. By eliminating regulatory receptors, cytokines, and cell populations from this system, we provide evidence for a two\u2010staged process. Parasite products first engage the TGF\u2010\u03b2 receptor on host\u2010derived T cells that are central to suppression. In a second step, host\u2010derived T cells produce IL\u201010 and subsequently suppress the adoptively transferred OT\u2010II T cells. Terminal suppression was IL\u201010\u2010dependant but independent of intrinsic TGF\u2010\u03b2 receptor\u2010 or PD\u20101\u2010mediated signaling in the suppressed OT\u2010II T cells. Blockade of the same key suppression mediators, i.e. TGF\u2010\u03b2\u2010 and IL\u201010 receptor, also ameliorated the suppression of IgG response to bystander antigen vaccination in <jats:italic>L. sigmodontis<\/jats:italic>\u2010infected mice.<\/jats:p>","DOI":"10.1002\/eji.201545503","type":"journal-article","created":{"date-parts":[[2015,7,3]],"date-time":"2015-07-03T15:55:23Z","timestamp":1435938923000},"page":"2568-2581","source":"Crossref","is-referenced-by-count":24,"title":["<i>Litomosoides sigmodontis<\/i> induces TGF\u2010\u03b2 receptor responsive, IL\u201010\u2010producing T cells that suppress bystander T\u2010cell proliferation in mice"],"prefix":"10.1002","volume":"45","author":[{"given":"Wiebke","family":"Hartmann","sequence":"first","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Schramm","sequence":"additional","affiliation":[{"name":"University Hospital Hamburg Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minka","family":"Breloer","sequence":"additional","affiliation":[{"name":"Bernhard Nocht Institute for Tropical Medicine  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,24]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI34261"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.05040-11"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/491183a"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2012.10.016"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2008.02.009"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.2006.00854.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2007.05.006"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.03.078"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.11.019"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051512"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2004.09.038"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2014.07.107"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.4.2138-2144.2006"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.02.055"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-4758(00)01738-5"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000217"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201141955"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1004136"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003170"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115611"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003215"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20101074"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00286.2002"},{"key":"e_1_2_7_25_1","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.4049\/jimmunol.142.5.1536","article-title":"Monoclonal antibodies recognizing transforming growth factor\u2010beta. 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