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Cyclophilin D (CypD) is a mitochondrial matrix protein that modulates the mitochondrial permeability transition pore, but its role in IFN-I signaling and CD8+ T cell responses to viral infection has not been previously explored. In this study, we demonstrate that CypD plays a critical extrinsic role in the survival of Ag-specific CD8+ T cell following acute viral infection with lymphocytic choriomeningitis virus in mice. CypD deficiency resulted in reduced IFN-I and increased CD8+ T cell death, resulting in a reduced antiviral CD8+ T cell response. In addition, CypD deficiency was associated with an increase in pathogen burden at an early time-point following infection. Furthermore, our data demonstrate that transfer of wild-type macrophages (expressing CypD) to CypD-deficient mice can partially restore CD8+ T cell responses. These results establish that CypD plays an extrinsic role in regulating optimal effector CD8+ T cell responses to viral infection. Furthermore, this suggests that, under certain circumstances, inhibition of CypD function may have a detrimental impact on the host\u2019s ability to respond to viral infection.<\/jats:p>","DOI":"10.4049\/immunohorizons.2000016","type":"journal-article","created":{"date-parts":[[2020,4,24]],"date-time":"2020-04-24T20:25:12Z","timestamp":1587759912000},"page":"217-230","source":"Crossref","is-referenced-by-count":5,"title":["Cyclophilin D Regulates Antiviral CD8+ T Cell Survival in a Cell-Extrinsic Manner"],"prefix":"10.1093","volume":"4","author":[{"given":"Stephanie A","family":"Condotta","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, McGill University , Montreal, Quebec H3G 1Y6 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Downey","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, McGill University , Montreal, Quebec H3G 1Y6 ,","place":["Canada"]},{"name":"Meakins-Christie Laboratories, McGill University Health Centre , Montreal, Quebec H4A 3J1 ,","place":["Canada"]},{"name":"Department of Medicine, McGill University Health Centre , Montreal, Quebec H4A 3J1 ,","place":["Canada"]},{"name":"Department of Pathology, McGill University Health Centre , Montreal, Quebec H4A 3J1 ,","place":["Canada"]},{"name":"McGill International TB Centre, McGill University Health Centre , Montreal, Quebec H4A 3J1 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan D","family":"Pardy","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, McGill University , Montreal, Quebec H3G 1Y6 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie F","family":"Valbon","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, McGill University , Montreal, Quebec H3G 1Y6 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"Tarrab","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Immunovirologie, Institut National de la Recherche Scientifique, Institut National de la Recherche Scientifique-Institut Armand-Frappier , Laval, Quebec H7V 1B7 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7913-871X","authenticated-orcid":false,"given":"Alain","family":"Lamarre","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Immunovirologie, Institut National de la Recherche Scientifique, Institut National de la Recherche Scientifique-Institut Armand-Frappier , Laval, Quebec H7V 1B7 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