Changes in immune responses to antigen applied to tape-stripped skin with CpG-oligodeoxynucleotide in NC/Nga mice

Purpose. CpG-oligodeoxynucleotide (CpG-ODN) plays a critical role in immunity via the augmentation of Th-1 and the suppression of Th-2 responses. We examined here the effect of CpG-ODN on the immune response to an antigen applied to a tape-stripped skin of NC/Nga mouse, a human atopic dermatitis (AD) model, by evaluating the production of cytokines and immunoglobulin isotypes. Methods. Model antigen, ovalbumin (OVA), and CpG-ODN were applied on to the shaved skin. The penetration of OVA and CpG-ODN was evaluated using confocal laser scanning microscopy (CLSM). Secretion of cytokine from splenocytes and changes in immunoglobulin isotype levels were determined by enzyme-linked immunosorbent assay (ELISA). Results. Through CLSM it was revealed that the model antigen, OVA, and CpG-ODN easily penetrated the tape-stripped skin. Coadministration of CpG-ODN and OVA to the skin elicited an antigen-specific, Th-1-predominant immune response and enhanced the production of IFN-gamma. On the other hand, the production of a Th-2-type cytokine, IL-4, was drastically suppressed. In terms of antigen-specific antibody production, the level of IgG2a regulated by IFN-gamma was increased by CpG-ODN, but IgE production regulated by IL-4 was suppressed. Conclusions. Administration of CpG-ODN with antigen through the skin may shift the immune response from a Th-2- to Th-1-like response. These results suggested that administration of CpG-ODN via skin is a simple strategy for patients with diseases such as AD, which is characterized by Th-2-dominated inflammation.