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The present study found that in vivo overexpression of IL-27 in mice led to increased T cell expression of PD-L1, LAG-3, TIGIT, and TIM-3. In vitro, TCR stimulation alone promoted expression of multiple IRs, whereas IL-27 alone induced expression of PD-L1. However, the combination of intermediate TCR stimulation and IL-27 resulted in synergistic induction of LAG-3, CTLA-4, and TIGIT. In vivo, infection with Toxoplasma gondii resulted in parasite-specific effector T cells that expressed high levels of IR, and at local sites of infection where IL-27 production was highest, IL-27 was required for maximal effector cell expression of PD-L1, LAG-3, CTLA-4, and TIGIT. Together, these results affirm the critical role of TCR signals in the induction of IR expression but find that during infection, IL-27 promotes T cell expression of IR.<\/jats:p>","DOI":"10.4049\/immunohorizons.1800083","type":"journal-article","created":{"date-parts":[[2019,1,15]],"date-time":"2019-01-15T21:35:24Z","timestamp":1547588124000},"page":"13-25","source":"Crossref","is-referenced-by-count":80,"title":["IL-27 and TCR Stimulation Promote T Cell Expression of Multiple Inhibitory Receptors"],"prefix":"10.1093","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2032-8228","authenticated-orcid":false,"given":"Jonathan H","family":"DeLong","sequence":"first","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisling","family":"O\u2019Hara Hall","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA 19104"},{"name":"Immunology Discovery Research, Janssen Research and Development, LLC , Spring House, PA 19477"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Rausch","sequence":"additional","affiliation":[{"name":"Surface Oncology , Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devapregasan","family":"Moodley","sequence":"additional","affiliation":[{"name":"Surface Oncology , Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Perry","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeongho","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2935-6070","authenticated-orcid":false,"given":"Anthony T","family":"Phan","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P","family":"Beiting","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross M","family":"Kedl","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado , Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A","family":"Hill","sequence":"additional","affiliation":[{"name":"Surface Oncology , Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A","family":"Hunter","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,1,16]]},"reference":[{"key":"2025010607474451000_r1","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nri3405","article-title":"Molecular mechanisms of T cell co-stimulation and co-inhibition. 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