{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:33:02Z","timestamp":1791387182562,"version":"4.3.3"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2014,6,1]],"date-time":"2014-06-01T00:00:00Z","timestamp":1401580800000},"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":[[2014,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Memory-phenotype CD8+ T cells can arise even in the absence of overt Ag stimulation. Virtual memory (VM) CD8+ T cells are CD8+ T cells that develop a memory phenotype in the periphery of wild-type mice in an IL-15\u2013dependent manner. Innate CD8+ T cells, in contrast, are memory-phenotype CD8+ T cells that develop in the thymus in response to elevated thymic IL-4. It is not clear whether VM cells and innate CD8+ T cells represent two independent T cell lineages or whether they arise through similar processes. In this study, we use mice deficient in Nedd4-family interacting protein 1 to show that overproduction of IL-4 in the periphery leads to an expanded VM population. Nedd4-family interacting protein 1\u2212\/\u2212 CD4+ T cells produce large amounts of IL-4 due to a defect in JunB degradation. This IL-4 induces a memory-like phenotype in peripheral CD8+ T cells that includes elevated expression of CD44, CD122, and Eomesodermin and decreased expression of CD49d. Thus, our data show that excess peripheral IL-4 is sufficient to cause an increase in the VM population. Our results suggest that VM and innate CD8+ T cells may be more similar than previously appreciated.<\/jats:p>","DOI":"10.4049\/jimmunol.1301755","type":"journal-article","created":{"date-parts":[[2014,5,3]],"date-time":"2014-05-03T06:22:05Z","timestamp":1399098125000},"page":"5643-5651","source":"Crossref","is-referenced-by-count":35,"title":["Increased Peripheral IL-4 Leads to an Expanded Virtual Memory CD8+ Population"],"prefix":"10.1093","volume":"192","author":[{"given":"Vanessa","family":"Kurzweil","sequence":"first","affiliation":[{"name":"Cell and Molecular Biology Program, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ami","family":"LaRoche","sequence":"additional","affiliation":[{"name":"Cell Pathology Division, Department of Pathology and Laboratory Medicine, Children\u2019s Hospital of Philadelphia, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula M","family":"Oliver","sequence":"additional","affiliation":[{"name":"Cell and Molecular Biology Program, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104"},{"name":"Cell Pathology Division, Department of Pathology and Laboratory Medicine, Children\u2019s Hospital of Philadelphia, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,6,15]]},"reference":[{"key":"2025032404354367100_r1","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.immuni.2008.11.002","article-title":"Homeostasis of naive and memory T cells","volume":"29","author":"Surh","year":"2008","journal-title":"Immunity"},{"key":"2025032404354367100_r2","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.immuni.2009.11.007","article-title":"Diversity in T cell memory: an embarrassment of riches","volume":"31","author":"Jameson","year":"2009","journal-title":"Immunity"},{"key":"2025032404354367100_r3","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1084\/jem.192.4.549","article-title":"Homeostasis-stimulated proliferation drives naive T cells to differentiate directly into memory T cells","volume":"192","author":"Cho","year":"2000","journal-title":"J. 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