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However, DNA priming is known to have limited efficacy; therefore in the current study the effect of NKT cell activation using \u03b1\u2010galactosyl\u2010ceramide (\u03b1GalCer) during intradermal DNAp36 priming was examined. Vaccinated mice receiving \u03b1GalCer\u2004+ DNAp36 followed by a boost with VVp36 appeared to be resolving their lesions and had at ten\u2010 to 20\u2010fold higher reductions in parasite burdens. NKT cell activation during \u03b1GalCer\u2004+ DNAp36 priming resulted in higher numbers of antigen\u2010reactive effector CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells producing granzyme and IFN\u2010\u03b3, with lower levels of IL\u201010. Although immunodepletion studies indicate that both CD4 and CD8 T cells provide protection in the vaccinated mice, the contribution of CD4<jats:sup>+<\/jats:sup> T cells was significantly increased in mice primed with DNAp36 together with \u03b1GalCer. Notably 5\u2004months after boosting, mice vaccinated with DNAp36\u2004+ \u03b1GalCer continued to show sustained and heightened T cell immune responses. Thus, heterologous prime\u2010boost vaccination using \u03b1GalCer during priming is highly protective against murine cutaneous leishmaniasis, resulting in the heightened activation and development of CD4 and CD8 T cells (effector and memory T cells).<\/jats:p>","DOI":"10.1002\/eji.200737660","type":"journal-article","created":{"date-parts":[[2008,2,19]],"date-time":"2008-02-19T14:00:27Z","timestamp":1203429627000},"page":"706-719","source":"Crossref","is-referenced-by-count":39,"title":["Intradermal NKT cell activation during DNA priming in heterologous prime\u2010boost vaccination enhances T cell responses and protection against 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