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However, the mechanisms involved in the induction and maintenance of CD8<jats:sup>+<\/jats:sup>CTL memory are currently poorly understood. In this study, we investigated the involvement of CD40 ligand (CD40L)-mediated interactions in these processes by analyzing the memory CTL response of CD40L-deficient mice following infection with lymphocytic choriomeningitis virus (LCMV). The maintenance of memory CD8<jats:sup>+<\/jats:sup>CTL precursors (CTLp) at stable frequencies over time was not impaired in CD40L-deficient mice. By contrast, the initial generation of memory CTLp was affected. CD40L-deficient mice produced lower levels of CD8<jats:sup>+<\/jats:sup>CTLp during the primary immune response to LCMV than did wild-type controls, despite the fact that the LCMV-specific effector CTL response of CD40L-deficient mice was indistinguishable from that of control animals. The differentiation of na\u0131\u0308ve CD8<jats:sup>+<\/jats:sup>T cells into effector and memory CTL thus involves pathways that can be discriminated from each other by their requirement for CD40L-mediated interactions. Expression of CD40L by CTLp themselves was not an essential step during their expansion and differentiation from na\u0131\u0308ve CD8<jats:sup>+<\/jats:sup>cells into memory CTLp; instead, the reduction in memory CTLp generation in CD40L-deficient mice was likely a consequence of defects in the CD4<jats:sup>+<\/jats:sup>T-cell response mounted by these animals. These results thus suggest a previously unappreciated role for CD40L in the generation of CD8<jats:sup>+<\/jats:sup>memory CTLp, the probable nature of which is discussed.<\/jats:p>","DOI":"10.1128\/jvi.72.9.7440-7449.1998","type":"journal-article","created":{"date-parts":[[2019,12,31]],"date-time":"2019-12-31T18:17:43Z","timestamp":1577816263000},"page":"7440-7449","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":83,"title":["CD40 Ligand-Mediated Interactions Are Involved in the Generation of Memory CD8<sup>+<\/sup>Cytotoxic T Lymphocytes (CTL) but Are Not Required for the Maintenance of CTL Memory following Virus Infection"],"prefix":"10.1128","volume":"72","author":[{"given":"Persephone","family":"Borrow","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Division of Virology, Department of Neuropharmacology,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F.","family":"Tough","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Department of Immunology,2 The Scripps Research Institute, La Jolla, California 92037, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danelle","family":"Eto","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Division of Virology, Department of Neuropharmacology,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoinette","family":"Tishon","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Division of Virology, Department of Neuropharmacology,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iqbal S.","family":"Grewal","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Section of Immunobiology, Howard Hughes Medical Institute Research Laboratories, Yale University School of Medicine, New Haven, Connecticut 065103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Sprent","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Department of Immunology,2 The Scripps Research Institute, La Jolla, California 92037, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Flavell","sequence":"additional","affiliation":[{"name":"<!--label omitted: 3-->Section of Immunobiology, Howard Hughes Medical Institute Research Laboratories, Yale University School of Medicine, New Haven, Connecticut 065103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B. 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