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U.S.A."],"published-print":{"date-parts":[[2002,10]]},"abstract":"<jats:p>\n                    Although a role for CD4\n                    <jats:sup>+<\/jats:sup>\n                    helper cells in CD8\n                    <jats:sup>+<\/jats:sup>\n                    cytotoxic T lymphocyte (CTL) induction by vaccines is widely recognized, much less is known about a counterbalancing role of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in down-modulating this response, or about ways to optimize vaccine responses through abrogation of this negative regulatory mechanism. Here, we discovered a synergistic enhancement of vaccine-mediated CTL induction and protection by the relief of suppression through depletion of regulatory CD4\n                    <jats:sup>+<\/jats:sup>\n                    cells, including CD4\n                    <jats:sup>+<\/jats:sup>\n                    NKT cells, or blockade of IL-13 made by these cells, combined with the cytokine granulocyte\/macrophage colony-stimulating factor and the costimulatory molecule CD40L. Indeed, in the absence of helper epitopes, granulocyte\/macrophage colony-stimulating factor and the helper-mimetic molecule CD40L are not sufficient to replace help to induce CTL without abrogation of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell-mediated suppression, suggesting a role for T cell help in overcoming suppression. The increased CTL induction translated to striking protection against viral infection by a vaccine by using this synergistic combined approach. These results argue for a push\u2013pull approach to maximize vaccine efficacy, especially for HIV and cancer.\n                  <\/jats:p>","DOI":"10.1073\/pnas.192251199","type":"journal-article","created":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T12:58:28Z","timestamp":1033477108000},"page":"13020-13025","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":73,"title":["A push\u2013pull approach to maximize vaccine efficacy: Abrogating suppression with an IL-13 inhibitor while augmenting help with granulocyte\/macrophage colony-stimulating factor and CD40L"],"prefix":"10.1073","volume":"99","author":[{"given":"Jeffrey D.","family":"Ahlers","sequence":"first","affiliation":[{"name":"Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Wyeth Genetics Institute, Andover, MA 01810; and Immunex Corporation, Seattle, WA 98101-2936"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor M.","family":"Belyakov","sequence":"additional","affiliation":[{"name":"Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Wyeth Genetics Institute, Andover, MA 01810; and Immunex Corporation, Seattle, WA 98101-2936"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Terabe","sequence":"additional","affiliation":[{"name":"Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Wyeth Genetics Institute, Andover, MA 01810; and Immunex Corporation, Seattle, WA 98101-2936"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rima","family":"Koka","sequence":"additional","affiliation":[{"name":"Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Wyeth Genetics Institute, Andover, MA 01810; and Immunex Corporation, Seattle, WA 98101-2936"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra D.","family":"Donaldson","sequence":"additional","affiliation":[{"name":"Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Wyeth Genetics Institute, Andover, MA 01810; and Immunex Corporation, Seattle, WA 98101-2936"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine K.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Wyeth Genetics Institute, Andover, MA 01810; and Immunex Corporation, Seattle, WA 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