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Publication : Enhanced contact hypersensitivity in human monocyte chemoattractant protein-1 transgenic mouse.

First Author  Mizumoto N Year  2001
Journal  Immunobiology Volume  204
Issue  4 Pages  477-93
PubMed ID  11776402 Mgi Jnum  J:128164
Mgi Id  MGI:3766351 Doi  10.1078/0171-2985-00057
Citation  Mizumoto N, et al. (2001) Enhanced contact hypersensitivity in human monocyte chemoattractant protein-1 transgenic mouse. Immunobiology 204(4):477-93
abstractText  Monocyte chemoattractant protein (MCP)-1 is a chemotactic cytokine for monocytes, memoryT cells and dendritic cells (DC). However, the precise role of MCP-1 in a variety of immunological responses remains unclear. In the present study, we analyzed contact hypersensitivity (CHS) using human MCP-1 transgenic mice (hMCP-1Tgm) that constitutively produce high levels of hMCP-1 in the sera. Following 2,4-dinitrofluorobenzene (DNFB) sensitization, enhancement of CHS was demonstrated in Tgm as compared with that in non-Tgm. Anti-hMCP-1 antibodies significantly inhibited the CHS in Tgm. A prominent accumulation of B7-1+I-Ad+ Langerhans' cells (LC) bearing haptens was detected in draining lymph nodes (DLN) of Tgm 24 h after DNFB or fluorescein isothiocyanate (FITC) sensitization. Similar results were obtained with BALB/c mice administrated recombinant (r) hMCP-1. Langerhans' cells (LC) in the epidermal sheets of Tgm increased in size and expressed high levels of I-Ad and B7-1 12 h after FITC application compared with those of non-Tgm. After 18 h, the number of LC in the epidermis was reduced in Tgm. It was also shown that the B7-1 expression on LC of BALB/c mice was augmented after culture with rhMCP-1. These findings demonstrate that MCP-1 not only accelerates LC migration from epidermis into the DLN after sensitization with haptens but also up-regulates the I-Ad and B7-1 expressions, which results in the enhanced T cell activation and CHS.
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