Enhanced contact hypersensitivity in human monocyte chemoattractant protein-1 transgenic mouse.
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.
Mizumoto
N
N
Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
Iwabichi
K
K
Nakamura
H
H
Ato
M
M
Shibaki
A
A
Kawashima
T
T
Kobayashi
H
H
Iwabuchi
C
C
Ohkawara
A
A
Onoé
K
K
D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology*; D004139:Dinitrofluorobenzene / Q000276:immunology / Q000494:pharmacology; D006241:Haptens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology; D007700:Kinetics; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology; D015854:Up-Regulation
D018122:B7-1 Antigen; D018932:Chemokine CCL2; D006241:Haptens; D000949:Histocompatibility Antigens Class II; C111389:I-Ad antigen; D004139:Dinitrofluorobenzene