1. ¹Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
2. ²Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan

Correspondence: Dr Akimichi Morita, Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. E-mail: amorita@med.nagoya-cu.ac.jp

Received 1 March 2005; Revised 3 September 2005; Accepted 11 September 2005.

Abstract

Activation and maturation of dendritic cells (DC) are crucial for the establishment of delayed-type hypersensitivity (DTH). However, antigen presentation by immature DC (iDC) might lead to antigen-specific peripheral tolerance. NF-B plays significant roles in upregulation of co-stimulatory molecules and cytokines in DC and therefore we investigated whether NF-B decoy oligodeoxynucleotide (ODN) might induce tolerance to DTH. NF-B decoy ODN suppressed ovalbumin (OVA)-induced DTH responses not only in naïve but also in presensitized mice. The suppressive effect was found to be antigen-specific. NF-B decoy ODN-induced tolerance involved CD4⁺CD25⁺ regulatory T cells (Treg), because in vivo depletion of CD25⁺ T cells abrogated the tolerance, whereas adoptive transfer of such T cell population from tolerant mice induced tolerance. Furthermore, the induction of Treg was related to insufficient migration and/or maturation of DC, because a sizable DC population still remained in peripheral tissue even after exposure to exogenous antigen in NF-B decoy ODN-treated mice. Even if they migrated into lymph nodes, they showed insufficient upregulation of co-stimulatory molecules and impaired antigen-specific activation of T cells. Topical application of NF-B decoy ODN might thus be a new approach to induce antigen-specific peripheral tolerance.