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However, the antigen specificity and functional properties of these cells is poorly defined. In this study, we show that IL-4 regulates not only the frequency and function of innate memory CD8+ T cells, but also regulates Eomes expression levels and functional reactivity of naive CD8+ T cells. Lack of IL-4 responsiveness attenuates the capacity of CD8+ T cells to mount a robust response to lymphocytic choriomeningitis virus infection, with both quantitative and qualitative effects on effector and memory antigen-specific CD8+ T cells. Unexpectedly, we found that, although numerically rare, memory phenotype CD8+ T cells in IL-4R\u03b1\u2013deficient mice exhibited enhanced reactivity after in vitro and in vivo stimulation. Importantly, our data revealed that these effects of IL-4 exposure occur before, not during, infection. Together, these data show that IL-4 influences the entire peripheral CD8+ T cell pool, influencing expression of T-box transcription factors, functional reactivity, and the capacity to respond to infection. These findings indicate that IL-4, a canonical Th2 cell cytokine, can sometimes promote rather than impair Th1 cell\u2013type immune responses.<\/jats:p>","DOI":"10.1084\/jem.20151359","type":"journal-article","created":{"date-parts":[[2016,6,13]],"date-time":"2016-06-13T14:21:59Z","timestamp":1465827719000},"page":"1319-1329","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":58,"title":["IL-4 sensitivity shapes the peripheral CD8+ T cell pool and response to infection"],"prefix":"10.1084","volume":"213","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4000-3356","authenticated-orcid":false,"given":"Kristin R.","family":"Renkema","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4476-725X","authenticated-orcid":false,"given":"June-Yong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You Jeong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara E.","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9963-5687","authenticated-orcid":false,"given":"Kristin A.","family":"Hogquist","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"Jameson","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2016,6,13]]},"reference":[{"key":"2023072603350274200_bib1","doi-asserted-by":"publisher","first-page":"2516","DOI":"10.4049\/jimmunol.1102213","article-title":"Derivation and maintenance of virtual memory CD8 T cells","volume":"188","author":"Akue","year":"2012","journal-title":"J. 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