Further characterization of UVB radiation effects on Langerhans cells: altered expression of the costimulatory molecules B7-1 and B7-2.
We have reported previously that low-dose UVB radiation (UVBR, 50-200 J/m2) perturbs the antigen-presenting cell (APC) function of murine Langerhans cells (LC) by interfering with yet undefined costimulatory signals. In this study, we investigated (1) the effects of UVBR on the expression of the costimulatory molecules B7-1 and B7-2 on murine LC, (2) the functional consequences of defective B7-1 and B7-2 signalling on primary and secondary T-cell responses induced by LC and (3) the mechanism by which UVBR interferes with B7-1 and B7-2 expression. Ultraviolet-B radiation dose-dependently inhibited the culture-induced upregulation of B7-1 and B7-2 on LC from both UVB-susceptible (UVBs, C57BL/6) and UVB-resistant (UVBR, Balb/c) mice and abrogated their capacity to stimulate proliferation of naive alloreactive T cells and of the KLH (keyhole limpet hemocyanin)-specific T helper (Th)1 clone HDK-1. The UVBR-induced suppression of B7-1 and B7-2 on LC and their perturbed APC function were related, because exogenous triggering of the B7/CD28 pathway with a stimulatory monoclonal antibody (mAb) for CD28 to UVB-irradiated LC partially restored T-cell proliferation. Such reconstitution was not observed when the mAb was added to killed LC, indicating that the UVBR-induced suppression of APC function was not due to lethal effects on LC. Conditioned supernatants from UVB-irradiated epidermal cells did not inhibit the functional upregulation of B7-1 and B7-2, suggesting that UVBR inhibits B7-1 and B7-2 upregulation by acting directly on LC and not by altering LC costimulatory function via release of soluble immunosuppressive factors. In conclusion, UVBR distorts the functional expression of B7-1 and B7-2 on LC from both UVBS and UVBR mice, thereby contributing to the failure of UVB-irradiated LC to stimulate resting alloreactive T cells or KLH-specific Th1 cells.
Denfeld
R W
RW
Department of Dermatology, Albert-Ludwigs-Universität, Freiburg, Germany. Denfeld@hau1.ukl.uni-freiburg.de
Tesmann
J P
JP
Dittmar
H
H
Weiss
J M
JM
Schöpf
E
E
Weltzien
H U
HU
Simon
J C
JC
D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D018122:B7-1 Antigen / Q000235:genetics*; D051940:B7-2 Antigen; D004307:Dose-Response Relationship, Radiation; D005260:Female; D007515:Islets of Langerhans / Q000528:radiation effects*; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014466:Ultraviolet Rays
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins