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Whilst the dynamics of CD8<jats:sup>+<\/jats:sup> T\u2010cell activation and migration during extant primary PbA infection have been extensively researched, the fate of the parasite\u2010specific CD8<jats:sup>+<\/jats:sup> T cells upon resolution of ECM is not understood. In this study, we show that memory OT\u2010I cells persist systemically within the spleen, lung and brain following recovery from ECM after primary PbA\u2010OVA infection. Whereas memory OT\u2010I cells within the spleen and lung exhibited canonical central memory (Tcm) and effector memory (Tem) phenotypes, respectively, memory OT\u2010I cells within the brain post\u2010PbA\u2010OVA infection displayed an enriched CD69<jats:sup>+<\/jats:sup>CD103<jats:sup>\u2212<\/jats:sup> profile and expressed low levels of T\u2010bet. OT\u2010I cells within the brain were excluded from short\u2010term intravascular antibody labelling but were targeted effectively by longer\u2010term systemically administered antibodies. Thus, the memory OT\u2010I cells were extravascular within the brain post\u2010ECM but were potentially not resident memory cells. Importantly, whilst memory OT\u2010I cells exhibited strong reactivation during secondary PbA\u2010OVA infection, preventing activation of new primary effector T cells, they had dampened reactivation during a fourth PbA\u2010OVA infection. Overall, our results demonstrate that memory CD8<jats:sup>+<\/jats:sup> T cells are systemically distributed but exhibit a unique phenotype within the brain post\u2010ECM, and that their reactivation characteristics are shaped by infection history. Our results raise important questions regarding the role of distinct memory CD8<jats:sup>+<\/jats:sup> T\u2010cell populations within the brain and other tissues during repeat <jats:italic>Plasmodium<\/jats:italic> infections.<\/jats:p>","DOI":"10.1111\/imm.13405","type":"journal-article","created":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T19:38:50Z","timestamp":1629315530000},"page":"737-753","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Memory CD8<sup>+<\/sup> T cells exhibit tissue imprinting and non\u2010stable exposure\u2010dependent reactivation characteristics following blood\u2010stage <i>Plasmodium berghei<\/i> ANKA infections"],"prefix":"10.1111","volume":"164","author":[{"given":"Tovah N.","family":"Shaw","sequence":"first","affiliation":[{"name":"Faculty of Biology, Medicine and Health The Lydia Becker Institute of Immunology and Inflammation University of Manchester Manchester UK"},{"name":"School of Biological Sciences Institute of Immunology and Infection University of Edinburgh Edinburgh UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Haley","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health The Lydia Becker Institute of Immunology and Inflammation University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca S.","family":"Dookie","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health The Lydia Becker Institute of Immunology and Inflammation University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenna J.","family":"Godfrey","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health The Lydia Becker Institute of Immunology and Inflammation University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonn J.","family":"Cheeseman","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health The Lydia Becker Institute of Immunology and Inflammation University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Strangward","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health The Lydia Becker Institute of Immunology and Inflammation University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leo A. 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