Ultraviolet B radiation sensitizes a murine epidermal dendritic cell line (XS52) to undergo apoptosis upon antigen presentation to T cells.
Ultraviolet B irradiation of skin leads to immunologic tolerance, rather than immunity against newly introduced Ag, by altering the function of Langerhans cells, skin-specific members of the dendritic cell (DC) family. Using the murine epidermal-derived DC line, XS52, which retains important features of resident Langerhans cells, we have tested the hypothesis that UV radiation delivers a signal leading to apoptosis. XS52 cells, when exposed to modest fluences (25-100 J/m2) of radiation, underwent apoptosis during a subsequent 6-h incubation with LPS or upon 6-h coculture with the keyhole limpet hemocyanin-specific Th1 clone HDK-1 in the presence of Ag. Specifically, XS52 cells treated in this way exhibited diminished cell viability, DNA laddering, and condensed staining of DNA. By contrast, none of these changes was induced by radiation alone, LPS alone, or coculture with T cells and Ag. Likewise, neither UV radiation plus T cells nor radiation plus Ag were sufficient to induce apoptosis, indicating that both T cells and Ag are required to induce apoptosis in the UV-sensitized cells. XS52 cells remained fully susceptible to T cell-mediated apoptosis even 16 h after irradiation, indicating the persistence of the sensitized state. These observations establish a model in which UV radiation induces a first event in which DC become sensitive to a second, apoptotic signal that is delivered by Ag-specific interaction with T cells or by LPS. We suggest that DC undergoing apoptosis deliver unusual activation signals to T cells during Ag presentation, signals that lead to cellular unresponsiveness rather than to effective immunity.
Kitajima
T
T
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Ariizumi
K
K
Bergstresser
P R
PR
Takashima
A
A
D000818:Animals; D017951:Antigen Presentation; D017209:Apoptosis / Q000528:radiation effects*; D002460:Cell Line; D007108:Immune Tolerance / Q000528:radiation effects; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology* / Q000528:radiation effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D015398:Signal Transduction; D012867:Skin / Q000276:immunology / Q000528:radiation effects; D013601:T-Lymphocytes / Q000276:immunology; D014466:Ultraviolet Rays
D008070:Lipopolysaccharides