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After acute viral infection, memory CD4+ T cells predominantly used residence to survey nonlymphoid tissues, albeit not as stringently as observed for CD8+ T cells. In contrast, memory CD4+ T cells were more likely to be resident within lymphoid organs than CD8+ T cells. Migration properties of memory-phenotype CD4+ T cells in non-SPF parabionts were similar, generalizing these results to diverse infections and conditions. CD4+ and CD8+ TRM shared overlapping transcriptional signatures and location-specific features, such as granzyme B expression in the small intestine, revealing tissue-specific and migration property\u2013specific, in addition to lineage-specific, differentiation programs. Functionally, mucosal CD4+ TRM reactivation locally triggered both chemokine expression and broad immune cell activation. Thus, residence provides a dominant mechanism for regionalizing CD4+ T cell immunity, and location enforces shared transcriptional, phenotypic, and functional properties with CD8+ T cells.<\/jats:p>","DOI":"10.1084\/jem.20181365","type":"journal-article","created":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T14:25:13Z","timestamp":1553783113000},"page":"1214-1229","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":208,"title":["CD4+ resident memory T cells dominate immunosurveillance and orchestrate local recall responses"],"prefix":"10.1084","volume":"216","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8597-3949","authenticated-orcid":true,"given":"Lalit K.","family":"Beura","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 1"},{"name":"Center for Immunology, University of Minnesota, Minneapolis, MN 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy J.","family":"Fares-Frederickson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 1"},{"name":"Center for Immunology, University of Minnesota, Minneapolis, MN 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6947-2271","authenticated-orcid":true,"given":"Elizabeth M.","family":"Steinert","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 1"},{"name":"Center for Immunology, University of Minnesota, Minneapolis, MN 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milcah C.","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 1"},{"name":"Center for Immunology, University of Minnesota, Minneapolis, MN 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily A.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 1"},{"name":"Center for Immunology, University of Minnesota, Minneapolis, MN 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn A.","family":"Fraser","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 1"},{"name":"Center for Immunology, University of Minnesota, Minneapolis, MN 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4641-6872","authenticated-orcid":true,"given":"Jason M.","family":"Schenkel","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 1"},{"name":"Center for Immunology, University of Minnesota, Minneapolis, MN 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2520-809X","authenticated-orcid":true,"given":"Vaiva","family":"Vezys","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 1"},{"name":"Center for Immunology, University of Minnesota, Minneapolis, MN 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9440-3884","authenticated-orcid":true,"given":"David","family":"Masopust","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 1"},{"name":"Center for Immunology, University of Minnesota, Minneapolis, MN 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2019,3,28]]},"reference":[{"key":"2023072604503769400_bib1","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1038\/s41385-018-0080-x","article-title":"Sustained protective immunity against Bordetella pertussis nasal colonization by intranasal immunization with a vaccine-adjuvant combination that induces IL-17-secreting TRM cells","volume":"11","author":"Allen","year":"2018","journal-title":"Mucosal Immunol."},{"key":"2023072604503769400_bib2","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/nprot.2014.005","article-title":"Intravascular staining for discrimination of vascular and tissue leukocytes","volume":"9","author":"Anderson","year":"2014","journal-title":"Nat. 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