Interleukin-12 prevents ultraviolet B-induced local immunosuppression and overcomes UVB-induced tolerance.
Ultraviolet (UV) light abrogates contact hypersensitivity (CHS) responses and induces hapten-specific tolerance. Because Th-1 cells are critically involved in CHS and are induced to develop by the cytokine interleukin (IL)-12, we asked whether IL-12 might overcome UV-induced local immunosuppression. C3H/HeN mice exposed to low doses of UV light over 4 d and hapten sensitized through the irradiated skin area with dinitrofluorobenzene showed profound inhibition of the CHS response, which was completely prevented upon intraperitoneal injection of murine recombinant IL-12 (rIL-12) after the last UV exposure. UV-treated mice resensitized 14 d after the first challenge displayed hapten-specific tolerance, whereas UV-exposed mice injected with rIL-12 before the first sensitization exhibited a vigorous CHS response. Furthermore, mice that were initially sensitized through UV-exposed skin also produced a significant CHS reaction when they received rIL-12 before resensitization. Adoptive transfer of spleen and lymph node cells from UV-irradiated mice treated with rIL-12 had no effect on the CHS response in recipient mice, whereas transfer of cells from UV-treated mice inhibited the immune response. These findings demonstrate that rIL-12 can prevent UV-induced local immunosuppression and overcome UV-induced hapten-specific tolerance.
Schwarz
A
A
Ludwig Boltzmann Institute for Cell Biology and Immuniobiology, Department of Dermatology, University Münster, Münster, Germany.
Grabbe
S
S
Aragane
Y
Y
Sandkuhl
K
K
Riemann
H
H
Luger
T A
TA
Kubin
M
M
Trinchieri
G
G
Schwarz
T
T
D000818:Animals; D006241:Haptens / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects*; D007165:Immunosuppression Therapy; D016219:Immunotherapy, Adoptive; D018664:Interleukin-12 / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D011994:Recombinant Proteins; D014466:Ultraviolet Rays
D006241:Haptens; D011994:Recombinant Proteins; D018664:Interleukin-12