Effects of ultraviolet B radiation on human Langerhans cells: functional alteration of CD86 upregulation and induction of apoptotic cell death.
We have recently reported that in vitro low dose of ultraviolet B radiation (UVB, 100-200 J per m2) directly impaired the antigen-presenting function of human Langerhans cells. In this study, we analyzed the effect of UVB irradiation on the Langerhans cells expression of several accessory molecules, namely CD54, CD80, and CD86. Langerhans cells phenotype was determined either immediately after UVB exposure (100 J per m2) or after a 2 d culture. No modification in cell surface antigen levels was observed immediately after irradiation. Prior UVB exposure did not modify the levels of CD80 at the Langerhans cells surface after a 2 d culture. In contrast, CD54 and, above all, CD86 expression were significantly decreased. Addition of exogenous anti-CD28 monoclonal antibodies partly restored the allostimulatory property of irradiated Langerhans cells in mixed epidermal cell-lymphocyte reaction, demonstrating that impairment of CD86 upregulation contributes to the UVB-induced immunosuppressive effect. Furthermore, we found that UVB irradiation at 200 J per m2 significantly reduced the number of viable Langerhans cells after 2 d of culture. UVB-induced cytotoxicity was due to apoptotic cell death, as demonstrated by typical morphologic alterations and by DNA fragmentation yielding a classical ladder pattern on gel electrophoresis. Interestingly, interaction of Langerhans cells with CD40-ligand transfected L cells improved the viability of irradiated Langerhans cells, counteracted the inhibition of CD86 expression, and efficiently reduced the number of apoptotic cells after a 2 d culture. Collectively, these results demonstrate that in vitro UVB exposure affects Langerhans cells via at least two distinct pathways: (i) decreased CD86 costimulatory molecule upregulation; and (ii) induction of Langerhans cells apoptosis, a phenomenon partly prevented by CD40 triggering.
Rattis
F M
FM
Laboratoire de Recherches Peau Humaine et Immunité, INSERM U346, Hôpital E. Herriot, Lyon, France.
Concha
M
M
Dalbiez-Gauthier
C
C
Courtellemont
P
P
Schmitt
D
D
Péguet-Navarro
J
J
D015703:Antigens, CD / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology / Q000528:radiation effects*; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000276:immunology; D002455:Cell Division / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D006801:Humans; D007801:Langerhans Cells / Q000473:pathology / Q000528:radiation effects*; D008562:Membrane Glycoproteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000528:radiation effects; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000528:radiation effects
D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D008562:Membrane Glycoproteins