Multiple solvent, N-methyl-2-pyrrolidone, acts as a novel adjuvant for enhancing cutaneous immune responses.

N-methyl-2-pyrrolidone (NMP) is known for its multi-solvent properties. However, its biological, especially immunological significance still remains to be elucidated. In this study, we show for the first time that NMP stimulates the skin immune system by activating epidermal Langerhans cells (LCs). In contrast with the placebo tape, when the NMP-containing adhesive tape was applied on murine skin, LCs were stimulated immediately. Activated LCs not only exhibited enhanced expression of major histocompatibility complex class II and morphological changes, including the loss of dendrites, but also migrated effectively to draining lymph nodes. In addition, application of the tyrosine-related protein-2 peptide, which is the cytotoxic T lymphocyte (CTL) epitope against B16 melanoma, in combination with the NMP tape, resulted in explosive expansion of specific CTLs in mouse spleens. Taken together, these results demonstrate a novel role of NMP as an adjuvant in percutaneous peptide immunization.