[Analysis of contact hypersensitivity response in human monocyte chemoattractant protein (MCP)-1 transgenic mice].

Epidermal Langerhans cells (LC) belong to the dendritic cell lineage and represent the major antigen-presenting cells (APC) within the skin. The molecular mechanisms responsible for LC migration to the skin have not fully been defined. MCP-1 is a cytokine of C-C chemokine subfamily that is chemotactic in vitro for monocytes, memory T cells and dendritic cells. In the present study, to examine the roles of LC and MCP-1 in hapten-induced contact hypersensitivity response (CHR), we utilized human MCP-1 transgenic mice (hMCP-1 Tgm) that produce constitutively high levels of hMCP-1 in the sera. Following DNFB sensitization, enhancement of CHR was demonstrated in Tgm as compared with CHR in non-Tgm at the entire period examined. Anti-hMCP-1 antibody significantly inhibited the DNFB-included CHR in Tgm. For analysis of the mechanisms underlying the enhanced CHR, migration and activation of LC were examined in Tgm and non-Tgm. The number of LC in the Tgm skin was within a normal range. However, the Tgm showed an accumulation of NLDC-145+ cells in the draining lymph nodes (DLN) 24 h after DNFB sensitization. When Tgm and non-Tgm were treated with FITC, the number of FITC+NLDC-145+ cells was larger in Tgm DLN than that in non-Tgm DLN 24 h after FITC application. Moreover, administration of recombinant hMCP-1 to BALB/c mice led to an increase of FITC+NLDC-145+ cells in the DLN. In addition, 12 h after application of FITC, LC in the epidermal sheets of Tgm increased in size and expressed high levels of I-Ad as compared with those of non-Tgm. Expression of B7-1 in 24h-cultured LC of BA LB/c mice was augmented by addition of recombinant hMCP-1 in a dose-dependent manner. These findings suggest that MCP-1 accelerates LC migration from epidermis into the DLN and up-regulates I-Ad and B7-1 expressions on the LC, which eventually enhances CHR.