{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T01:02:55Z","timestamp":1789779775524,"version":"4.0.1"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2011,8,1]],"date-time":"2011-08-01T00:00:00Z","timestamp":1312156800000},"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":[[2011,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The immune suppression that characterizes human helminth infections can hinder the development of protective immunity or help to reduce pathogenic inflammation. Signaling through the T cell costimulator glucocorticoid-induced TNFR-related protein (GITR) counteracts immune downregulation by augmenting effector T cell responses and abrogating suppression by Foxp3+ regulatory T cells. Thus, superphysiological Ab-mediated GITR costimulation represents a novel therapy for promoting protective immunity toward parasitic helminths, whereas blocking physiological GITR\u2013GITR ligand (GITRL) interactions may provide a mechanism for dampening pathogenic Th2 inflammation. We investigated the superphysiological and physiological roles of the GITR\u2013GITRL pathway in the development of protective and pathogenic Th2 responses in murine infection models of filariasis (Litomosoides sigmodontis) and schistosomiasis (Schistosoma mansoni). Providing superphysiological GITR costimulation using an agonistic anti-GITR mAb over the first 12 d of L. sigmodontis infection initially increased the quantity of Th2 cells, as well as their ability to produce Th2 cytokines. However, as infection progressed, the Th2 responses reverted to normal infection levels, and parasite killing remained unaffected. Despite the Th2-promoting role of superphysiological GITR costimulation, Ab-mediated blockade of the GITR\u2013GITRL pathway did not affect Th2 cell priming or maintenance during L. sigmodontis infection. Blockade of GITR\u2013GITRL interactions during the acute egg phase of S. mansoni infection resulted in reduced Th2 responses, but this effect was confined to the spleen and did not lead to changes in liver pathology. Thus, although superphysiological GITR costimulation can therapeutically enhance Th2 responses, physiological GITR\u2013GITRL interactions are not required for the development of Th2-mediated resistance or pathology in murine models of filariasis and schistosomiasis.<\/jats:p>","DOI":"10.4049\/jimmunol.1100834","type":"journal-article","created":{"date-parts":[[2011,6,25]],"date-time":"2011-06-25T23:17:02Z","timestamp":1309043822000},"page":"1411-1420","source":"Crossref","is-referenced-by-count":21,"title":["Th2 Responses to Helminth Parasites Can Be Therapeutically Enhanced by, but Are Not Dependent upon, GITR\u2013GITR Ligand Costimulation In Vivo"],"prefix":"10.1093","volume":"187","author":[{"given":"Nienke","family":"van der Werf","sequence":"first","affiliation":[{"name":"Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh , Edinburgh EH9 3JT ,","place":["United Kingdom"]},{"name":"Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh , Edinburgh EH9 3JT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A","family":"Redpath","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh , Edinburgh EH9 3JT ,","place":["United Kingdom"]},{"name":"Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh , Edinburgh EH9 3JT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander T","family":"Phythian-Adams","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh , Edinburgh EH9 3JT ,","place":["United Kingdom"]},{"name":"Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh , Edinburgh EH9 3JT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyuki","family":"Azuma","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Tokyo Medical and Dental University , Tokyo 113-8549 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith E","family":"Allen","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh , Edinburgh EH9 3JT ,","place":["United Kingdom"]},{"name":"Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh , Edinburgh EH9 3JT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick M","family":"Maizels","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh , Edinburgh EH9 3JT ,","place":["United Kingdom"]},{"name":"Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh , Edinburgh EH9 3JT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh , Edinburgh EH9 3JT ,","place":["United Kingdom"]},{"name":"Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh , Edinburgh EH9 3JT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D","family":"Taylor","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh , Edinburgh EH9 3JT ,","place":["United Kingdom"]},{"name":"Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh , Edinburgh EH9 3JT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,8,1]]},"reference":[{"key":"2025032410255860200_r1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.0105-2896.2004.00191.x","article-title":"Helminth parasites\u2014masters of regulation","volume":"201","author":"Maizels","year":"2004","journal-title":"Immunol. 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