{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:56:29Z","timestamp":1790092589043,"version":"4.0.1"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"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":[[2015,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Type I IFNs (IFN-I) are cytokines that can mediate both immune suppression and activation. Dendritic cells (DC) are significant producers of IFN-I, and depending on the context (nature of Ag, duration of exposure to Ag), DC-derived IFN-I can have varying effects on CD8+ T cell responses. In this study, we report that in the context of a CD8+ T cell response to a self-Ag, DC-intrinsic expression of IFN regulatory factor 3 is required to induce optimal proliferation and migration of autoreactive CD8+ T cells, ultimately determining their ability to infiltrate a target tissue (pancreas), and the development of glucose intolerance in rat insulin promoter\u2013glycoprotein (RIP-GP) mice. Moreover, we show that signals through the lymphotoxin-\u03b2 receptor (LT\u03b2R) in DC are also required for the proliferation of autoreactive CD8+ T cells, the upregulation of VLA4\/LFA1 on activated CD8+ T cells, and their subsequent infiltration into the pancreas both in vitro and in vivo. Importantly, the defects in autoreactive CD8+ T cell proliferation, accumulation of CD8+ T cells in the pancreas, and consequent glucose intolerance observed in the context of priming by LT\u03b2R\u2212\/\u2212 DC could be rescued by exogenous addition of IFN-I. Collectively, our data demonstrate that the LT\u03b2R\/IFN-I axis is essential for programming of CD8+ T cells to mediate immunopathology in a self-tissue. A further understanding of the IFN-I\/LT\u03b2R axis will provide valuable therapeutic insights for treatment of CD8+ T cell\u2013mediated autoimmune diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1501053","type":"journal-article","created":{"date-parts":[[2015,10,13]],"date-time":"2015-10-13T18:39:38Z","timestamp":1444761578000},"page":"4650-4659","source":"Crossref","is-referenced-by-count":9,"title":["A Lymphotoxin\/Type I IFN Axis Programs CD8+ T Cells To Infiltrate a Self-Tissue and Propagate Immunopathology"],"prefix":"10.1093","volume":"195","author":[{"given":"Dennis","family":"Ng","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 1A8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3264-7330","authenticated-orcid":false,"given":"Blandine","family":"Ma\u00eetre","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 1A8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Cummings","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University , Hamilton, Ontario L8S 4L8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Lin","sequence":"additional","affiliation":[{"name":"Campbell Family Cancer Research Institute, University Health Network , Toronto, Ontario M5G 2M9 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley A","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 1A8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramtin","family":"Rahbar","sequence":"additional","affiliation":[{"name":"Campbell Family Cancer Research Institute, University Health Network , Toronto, Ontario M5G 2M9 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L","family":"Mossman","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University , Hamilton, Ontario L8S 4L8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela S","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Campbell Family Cancer Research Institute, University Health Network , Toronto, Ontario M5G 2M9 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L","family":"Gommerman","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto , Toronto, Ontario M5S 1A8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,11,15]]},"reference":[{"key":"2025030704225166000_r1","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/nri1604","article-title":"Mechanisms of type-I- and type-II-interferon-mediated signalling","volume":"5","author":"Platanias","year":"2005","journal-title":"Nat. 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