CpG immunostimulatory sequences enhance contact hypersensitivity responses in mice

Hitoshi Akiba, Masataka Satoh, Keiji Iwatsuki, Dominique Kaiserlian, Jean François Nicolas, Fumio Kaneko

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Bacterial DNA and synthetic cytidine-phosphate-guanosine- oligodeoxynucleotides (CpG ODN) potently activate dendritic cells (DC) and therefore have been proposed as adjuvants for vaccination strategies. Although CpG ODN are considered as safe adjuvants this study shows that CpG ODN are responsible for enhanced antigen-specific skin inflammatory reactions. We used the murine model of contact hypersensitivity (CHS) to 2,4-dinitrofluorobenzene (DNFB) in which hapten-specific CD8+ T cytotoxic 1 cells are effector cells. Subcutaneous injection of CpG ODN, 1 d before sensitization enhanced the CHS response to DNFB and resulted in increased recruitment of CD8+ T cells at the challenge sites, whereas control ODH injection did not have any effect. This effect was local and not systemic as it was only observed when DNFB was applied at the same site as the CpG motifs. CpG ODN-induced enhancement of CHS was due to increased antigen-presenting cell functions of DC since: (i) CpG ODN-injected skin revealed upregulated expression of major histocompatibility complex class II, CD80, and CD86 molecules and (ii) CpG ODN treatment of DNFB-derivatized DC enhanced the intensity of CHS responses after in vivo transfer. Taken together, the results show that CpG ODN may be responsible for immune side-effects such as worsening of T cell-mediated skin diseases.

Original languageEnglish
Pages (from-to)488-493
Number of pages6
JournalJournal of Investigative Dermatology
Volume123
Issue number3
DOIs
Publication statusPublished - Sep 2004
Externally publishedYes

Keywords

  • Allergic contact
  • Antigens
  • Dermatitis
  • Immunotherapy
  • Mice

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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