1. ^*Department of Dermatology, Fukushima Medical University School of Medicine, Fukushima, Japan
2. ^†INSERM U503, IFR 128, and CH Lyon-Sud, UCB Lyon 1, France
3. ^‡INSERM U404, IFR 128, Lyon, France

Correspondence: Dr Hitoshi Akiba, Department of Dermatology, Fukushima Medical University School of Medicine, Hikarigaoka-1, Fukushima, 960-1295, Japan Email: hakiba@fmu.ac.jp

¹H.A. and M.S. contributed equally to this work.

²Current address: Department of Dermatology, Okayama University Graduate School of Medicine and Dentistry, Japan.

Received 20 January 2004; Revised 22 April 2004; Accepted 4 May 2004; Published online 6 August 2004.

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 ODN 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 hisotcompatibility 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.