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Adv."],"published-print":{"date-parts":[[2026,3,6]]},"abstract":"<jats:p>\n                    Memory CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells are central to long-term immunity, yet their persistence in the absence of antigen remains controversial. Lifelong immunity following cutaneous leishmaniasis is primarily mediated by CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, but whether persistent parasites are required for sustaining this immunity has not been empirically established. Using a nonpersistent\n                    <jats:italic toggle=\"yes\">Leishmania major<\/jats:italic>\n                    strain (\n                    <jats:italic toggle=\"yes\">dhfr-ts<\/jats:italic>\n                    \u2013deficient), we demonstrate that loss of antigen leads to a decline in\n                    <jats:italic toggle=\"yes\">Leishmania<\/jats:italic>\n                    -specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and susceptibility to reinfection. To elucidate the mechanism, we developed\n                    <jats:italic toggle=\"yes\">Leishmania<\/jats:italic>\n                    phosphoenolpyruvate carboxykinase (PEPCK)-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell receptor transgenic (PEG) mice, enabling precise tracking of\n                    <jats:italic toggle=\"yes\">Leishmania<\/jats:italic>\n                    -specific memory CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Both in vitro and in vivo\u2013generated memory PEG cells progressively declined in the absence of antigen, independent of major histocompatibility complex II expression. Mice infected with PEPCK antigen\u2013deficient\n                    <jats:italic toggle=\"yes\">L. major<\/jats:italic>\n                    failed to sustain recall responses and secondary immunity. These findings in a\n                    <jats:italic toggle=\"yes\">L. major<\/jats:italic>\n                    model system argue that persistent antigen may be indispensable for maintaining memory CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and ensuring durable immunity against chronic infections.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeb3345","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T18:58:52Z","timestamp":1772650732000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Persistent antigen is essential for sustaining\n                    <i>Leishmania major<\/i>\n                    \u2013specific memory CD4\n                    <sup>+<\/sup>\n                    T cells and long-term immunity"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0799-1137","authenticated-orcid":true,"given":"Zhirong","family":"Mou","sequence":"first","affiliation":[{"name":"Department of Immunology, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1934-1337","authenticated-orcid":true,"given":"Roma","family":"Zayats","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3032-4335","authenticated-orcid":true,"given":"Enitan","family":"Salako","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nnamdi","family":"Ikeogu","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7880-7961","authenticated-orcid":true,"given":"Somtochukwu S.","family":"Onwah","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1836-2267","authenticated-orcid":true,"given":"Dong","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute, Seattle, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6964-1020","authenticated-orcid":true,"given":"Hiroshi","family":"Hamana","sequence":"additional","affiliation":[{"name":"Department of Immunology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8740-5371","authenticated-orcid":true,"given":"Hiroyuki","family":"Kishi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7861-6786","authenticated-orcid":true,"given":"Da","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Faculty of Science, University of Manitoba, Winnipeg, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7541-9127","authenticated-orcid":true,"given":"Carson","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Faculty of Science, University of Manitoba, Winnipeg, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0220-0076","authenticated-orcid":true,"given":"Janilyn","family":"Arsenio","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada."},{"name":"Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3030-2726","authenticated-orcid":true,"given":"Thomas","family":"T. 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