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TVM cells from young individuals are highly proliferative in response to TCR and cytokine stimulation but, with age, they lose TCR-mediated proliferative capacity and exhibit hallmarks of senescence. Helminth infection can drive an increase in TVM cells, which is associated with improved pathogen clearance during subsequent infectious challenge in young mice. Given the cytokine-dependent profile of TVM cells and their age-associated dysfunction, we traced proliferative and functional changes in TVM cells, compared with true naive CD8 T cells, after helminth infection of young and aged C57BL\/6 mice. We show that IL-15 is essential for the helminth-induced increase in TVM cells, which is driven only by proliferation of existing TVM cells, with negligible contribution from true naive cell differentiation. Additionally, TVM cells showed the greatest proliferation in response to helminth infection and IL-15 compared with other CD8 T cells. Furthermore, TVM cells from aged mice did not undergo expansion after helminth infection due to both TVM cell\u2013intrinsic and \u2013extrinsic changes associated with aging.<\/jats:p>","DOI":"10.4049\/jimmunol.2200316","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T06:47:47Z","timestamp":1672728467000},"page":"297-309","source":"Crossref","is-referenced-by-count":19,"title":["Helminth Infection\u2013Induced Increase in Virtual Memory CD8 T Cells Is Transient, Driven by IL-15, and Absent in Aged Mice"],"prefix":"10.1093","volume":"210","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2672-2004","authenticated-orcid":false,"given":"Tabinda","family":"Hussain","sequence":"first","affiliation":[{"name":"Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University , Clayton, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1610-515X","authenticated-orcid":false,"given":"Angela","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University , Clayton, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmel","family":"Daunt","sequence":"additional","affiliation":[{"name":"Laboratory of Intestinal Immunology, Department of Immunology and Pathology, Central Clinical School, The Alfred Centre, Monash University , Melbourne, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4469-8215","authenticated-orcid":false,"given":"Daniel","family":"Thiele","sequence":"additional","affiliation":[{"name":"Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University , Clayton, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ee Shan","family":"Pang","sequence":"additional","affiliation":[{"name":"Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University , Clayton, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"Li","sequence":"additional","affiliation":[{"name":"Sir Peter MacCallum Department of Oncology, The University of Melbourne , Parkville, Victoria,","place":["Australia"]},{"name":"Cancer Immunology Program, Peter MacCallum Cancer Centre , Parkville, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aidil","family":"Zaini","sequence":"additional","affiliation":[{"name":"Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University , Clayton, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0779-4654","authenticated-orcid":false,"given":"Meredith","family":"O\u2019Keeffe","sequence":"additional","affiliation":[{"name":"Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University , Clayton, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9889-9848","authenticated-orcid":false,"given":"Colby","family":"Zaph","sequence":"additional","affiliation":[{"name":"Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University , Clayton, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2922-0210","authenticated-orcid":false,"given":"Nicola L","family":"Harris","sequence":"additional","affiliation":[{"name":"Laboratory of Intestinal Immunology, Department of Immunology and Pathology, Central Clinical School, The Alfred Centre, Monash University , Melbourne, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0417-3625","authenticated-orcid":false,"given":"Kylie M","family":"Quinn","sequence":"additional","affiliation":[{"name":"Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University , Clayton, Victoria,","place":["Australia"]},{"name":"School of Health and Biomedical Sciences, Royal Melbourne Institute of Technology University , Bundoora, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5358-9363","authenticated-orcid":false,"given":"Nicole L","family":"La Gruta","sequence":"additional","affiliation":[{"name":"Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University , Clayton, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,2,1]]},"reference":[{"key":"2025021007585200300_r1","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.immuni.2015.05.003","article-title":"The virome in host health and disease","volume":"42","author":"Cadwell","year":"2015","journal-title":"Immunity"},{"key":"2025021007585200300_r2","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.4049\/jimmunol.1800631","article-title":"The intestinal virome and 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