Deficient Th1-type immune responses via impaired CD28 signaling in ultraviolet B-induced systemic immunosuppression and the restorative effect of IL-12.
A single large dose (15 kJ/m(2)) of UVB-irradiation induces systemic immunosuppression and tolerance. We previously reported that IL-12 promotes the accessory cell function of epidermal Langerhans cells. In this study we have examined whether IL-12-pretreated antigen-presenting cells (APC) could restore the diminished T-cell response in mice irradiated with a single large dose of UVB. Spleen cells from UVB-irradiated mice showed reduced IFN-gamma production in a hapten-specific response but the function of APC in non-exposed skin of UVB-irradiated mice was not impaired. The pretreatment of APC with IL-12 did not restore the impaired IFN-gamma production by T cells from UVB-irradiated mice. Neither IL-10 nor TGF-beta was found to be involved in the suppression. Instead, we observed that anti-CD3 mAb-induced IFN-gamma production by T cells from UVB-irradiated mice was not augmented in the presence of anti-CD28 mAb, whereas IL-4 production was enhanced by the addition of anti-CD28 mAb. Furthermore, the reduced IFN-gamma production by T cells from UVB-irradiated mice in response to antigen plus APC could be restored by adding IL-12 to the culture. Our results thus indicate that UVB-induced systemic immunosuppression involves impaired Th1-type responses of T lymphocytes through CD28 stimulation, and that IL-12 compensates for the impaired CD28 costimulatory signaling in T cells resulting in the restoration of Th1-type responses.
Ando
O
O
Fujisaki Institute, Hayashibara Biochemical Laboratories, Inc., 675-1 Fujisaki, 702-8006, Okayama, Japan.
Suemoto
Y
Y
Kurimoto
M
M
Horikawa
T
T
Ichihashi
M
M
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000528:radiation effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D018106:CD28 Antigens / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects / Q000528:radiation effects; D007165:Immunosuppression Therapy; D018664:Interleukin-12 / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D014466:Ultraviolet Rays
D018106:CD28 Antigens; D018664:Interleukin-12