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The lineage relationships of these subpopulations as well as their involvement in protection have not yet been conclusively determined. We recently described a novel marker combination (CD127 and CD62L) to identify all three major CD8<jats:sup>+<\/jats:sup> T\u2004cell subsets in mice infected with <jats:italic>Listeria monocytogenes<\/jats:italic> <jats:italic>(L.m.)<\/jats:italic>. Extensive lineage relationship analyses on highly purified subpopulations after <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> stimulation demonstrated that T<jats:sub>CM<\/jats:sub> can develop into T<jats:sub>EM<\/jats:sub> or T<jats:sub>EC<\/jats:sub>, whereas T<jats:sub>EM<\/jats:sub> can only progress to T<jats:sub>EC<\/jats:sub> cells. Short\u2010living T<jats:sub>EC<\/jats:sub> never regained a T<jats:sub>EM<\/jats:sub> or T<jats:sub>CM<\/jats:sub> phenotype. These data strongly suggest a hierarchical and unidirectional order of developmental stages. <jats:italic>In vivo<\/jats:italic> priming protocols that preferentially induced one of the different CD8<jats:sup>+<\/jats:sup> T\u2004cell subsets demonstrated that predominance of T<jats:sub>EM<\/jats:sub> (CD40 stimulation) correlated best with effective protection against <jats:italic>L.m.<\/jats:italic>, whereas generation of neither T<jats:sub>CM<\/jats:sub> (by immunization with heat\u2010killed <jats:italic>L.m.<\/jats:italic>) nor T<jats:sub>EC<\/jats:sub> (by systemic co\u2010administration of CpG during primary infection) conferred substantial long\u2010term protective immunity. These findings have important implications for the design of more effective T\u2004cell\u2010based vaccines.<\/jats:p>","DOI":"10.1002\/eji.200635874","type":"journal-article","created":{"date-parts":[[2006,4,24]],"date-time":"2006-04-24T16:55:51Z","timestamp":1145897751000},"page":"1453-1464","source":"Crossref","is-referenced-by-count":79,"title":["Unidirectional development of CD8<sup>+<\/sup> central memory T\u2004cells into protective <i>Listeria<\/i>\u2010specific effector memory 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