Calcium channel blockers suppress the contact hypersensitivity reaction (CHR) by inhibiting antigen transport and presentation by epidermal Langerhans cells in mice

Since Langerhans cells (LC) are the principal antigen-presenting cells among epidermal cells, treatments suppressing LC function may inhibit CHR. Although calcium channel blockers (CCB) have been shown to suppress the functions of several immunologically active cells, little is known about their effect on LC. In this study we show that pretreatment with topical 1% nifedipine or verapamil HCl significantly suppressed both the sensitization and elicitation phases of a CHR in mice. We then investigated whether CCB affected LC. Flow cytometric analysis of regional lymph node cells obtained 24 h after applying FITC demonstrated that topical CCB treatment significantly reduced the percentage of FITC+ NLDC-145(+) cells, suggesting that CCB had suppressed antigen transport by LC. In vitro treatment with nifedipine or verapamil significantly suppressed the antigen-presenting capacity of LC in a dose-dependent manner. In addition, in vitro CCB treatment reduced the percentage of class II MHC antigen-positive epidermal cells and significantly suppressed class II MHC and B7-1 levels in LC, as determined by flow cytometry and reverse transcriptase-polymerase chain reaction, whereas surface expression of B7-2 and mRNA was only weakly reduced. Neither expression of CD45 nor the percentage of CD45(+) cells were affected, suggesting that the effects of CCB on LC were not due to cytotoxicity. Our results suggest that CCB inhibit CHR, at least in part, by suppressing the functions of LC.