Role of IL-2 secreted by PADRE-specific CD4+ T cells in enhancing E7-specific CD8+ T-cell immune responses

D. Kim, A. Monie, L. He, Y. C. Tsai, C. F. Hung, T. C. Wu

Research output: Contribution to journalArticle

Abstract

CD4+ T helper cells are known to play an integral role in the generation of CD8+ T-cell immune responses. We have previously shown that co-administration of DNA vaccines containing E6 or E7 protein of human papillomavirus 16 (HPV-16) combined with DNA encoding invariant (Ii) chain in which class II-associated Ii peptide (CLIP) region is replaced with the CD4+ T helper epitope, PADRE (Pan-DR-epitope) (Ii-PADRE DNA) enhanced HPV antigen-specific CD8+ T-cell immune responses in vaccinated mice. In the current study, we investigated the enhancement of HPV E7-specific CD8+ T-cell immune responses by PADRE-specific CD4+ T cells. We showed that intradermal administration of Ii-PADRE DNA at the same location as E7-expressing DNA is necessary to generate strong E7-specific CD8+ T-cell immune responses. We also showed that PADRE-specific CD4+ T cells generated by Ii-PADRE DNA vaccination expressed Th1 cytokine profile. Furthermore, our in vitro study demonstrated that PADRE-specific CD4+ T cells stimulated with PADRE-loaded dendritic cells secrete IL-2 that leads to the proliferation of E7-specific CD8+ T cells. Thus, our data suggest that activated PADRE-specific CD4+ T helper cells may be required at the vicinity of E7-specific CD8+ T cells where they secrete IL-2, which enhances the E7-specific CD8+ T-cell immune responses generated by DNA vaccination.

Original languageEnglish (US)
Pages (from-to)677-687
Number of pages11
JournalGene Therapy
Volume15
Issue number9
DOIs
StatePublished - May 1 2008

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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