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Here we demonstrate that the fractalkine-receptor\/CX<jats:sub>3<\/jats:sub>CR1 distinguishes memory CD8<jats:sup>+<\/jats:sup> T cells with cytotoxic effector function from those with proliferative capacity, independent of tissue-homing properties. CX<jats:sub>3<\/jats:sub>CR1-based transcriptome and proteome-profiling defines a core signature of memory CD8<jats:sup>+<\/jats:sup> T cells with effector function. We find CD62L<jats:sup>hi<\/jats:sup>CX<jats:sub>3<\/jats:sub>CR1<jats:sup>+<\/jats:sup> memory T cells that reside within lymph nodes. This population shows distinct migration patterns and positioning in proximity to pathogen entry sites. Virus-specific CX<jats:sub>3<\/jats:sub>CR1<jats:sup>+<\/jats:sup> memory CD8<jats:sup>+<\/jats:sup> T cells are scarce during chronic infection in humans and mice but increase when infection is controlled spontaneously or by therapeutic intervention. This CX<jats:sub>3<\/jats:sub>CR1-based functional classification will help to resolve the principles of protective CD8<jats:sup>+<\/jats:sup> T-cell memory.<\/jats:p>","DOI":"10.1038\/ncomms9306","type":"journal-article","created":{"date-parts":[[2015,9,25]],"date-time":"2015-09-25T09:20:05Z","timestamp":1443172805000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":308,"title":["Functional classification of memory CD8+ T cells by CX3CR1 expression"],"prefix":"10.1038","volume":"6","author":[{"given":"Jan P.","family":"B\u00f6ttcher","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9704-148X","authenticated-orcid":false,"given":"Marc","family":"Beyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1000-7989","authenticated-orcid":false,"given":"Felix","family":"Meissner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeinab","family":"Abdullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jil","family":"Sander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastian","family":"H\u00f6chst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Eickhoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan C.","family":"Rieckmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Russo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Flecken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Giesen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Engel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk H.","family":"Busch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Protzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Thimme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Mann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Kurts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim L.","family":"Schultze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Kastenm\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Percy A.","family":"Knolle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,9,25]]},"reference":[{"key":"BFncomms9306_CR1","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1146\/annurev.immunol.18.1.275","volume":"18","author":"JT Harty","year":"2000","unstructured":"Harty, J. 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