CD1a-positive dendritic cells transport the antigen DNCB intracellularly from the skin to the regional lymph nodes in the induction phase of allergic contact dermatitis.
Dendritic cells are potent stimulators of T cell-mediated immune responses. In contact hypersensitivity reactions in animals dendritic cells have been reported to transport antigens to the regional lymph nodes. In this study we investigated whether skin-derived dendritic cells transport contact antigens via the afferent lymph in humans. By means of a microsurgical technique lymph cells were collected after painting a defined skin region with a 2% concentration of the sensitizing agent 2,4-dinitrochlorobenzene on the leg of 14 volunteers. There was no significant change in flow, output or composition of cells after antigen painting. Using flow cytometric analysis we were able to detect the antigen in CD1a+ dendritic cells of the afferent lymph 15-25 h after antigen application. The antigen could only be detected after permeabilizing the dendritic cells, indicating that the main part of the antigen is transported intracellularly and not on the surface of these cells. Further analysis of cell surface antigens such as CD80, CD86, HLA-DR, CD11a, CD14, CD23, CD25 and CD54 revealed that in the course of cutaneous sensitization the phenotype of the dendritic cells was not altered in the afferent lymph. These results provide direct evidence that during the induction phase of allergic contact dermatitis in humans antigen-bearing dendritic cells internalize the antigen and migrate from the skin via the afferent lymph vessels to the lymph nodes.
Hunger
R E
RE
Dermatological Clinic, University of Berne, Switzerland. re.hunger@gmx.net
Yawalkar
N
N
Braathen
L R
LR
Brand
C U
CU
D000328:Adult; D018949:Antigens, CD1 / Q000378:metabolism*; D001692:Biological Transport; D015415:Biomarkers; D003713:Dendritic Cells / Q000378:metabolism*; D003877:Dermatitis, Contact / Q000276:immunology / Q000378:metabolism*; D004137:Dinitrochlorobenzene / Q000276:immunology / Q000493:pharmacokinetics*; D005434:Flow Cytometry; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008196:Lymph / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D008198:Lymph Nodes / Q000378:metabolism*; D008297:Male; D012867:Skin / Q000378:metabolism*
D018949:Antigens, CD1; D015415:Biomarkers; C419393:CD1a antigen; D004137:Dinitrochlorobenzene