Reduced IL-12 production by monocytes upon ultraviolet-B irradiation selectively limits activation of T helper-1 cells.
The capacity of APC to stimulate the proliferation of human peripheral blood T cells decreases upon ultraviolet-B (UVB) irradiation. The aim of this study was to investigate whether all T cell subsets are equally sensitive to this reduced APC function. Established human Th1, Th2, and Th0 clones were stimulated with monocytes in a soluble CD3 mAb-mediated assay that is dependent on the presence of APC. Monocytes were exposed to low nonlethal doses of UVB radiation before coculture with T cells. UVB irradiation inhibited the capacity of monocytes to stimulate the proliferation and IFN-gamma production of Th1 cells in a dose-related fashion. In contrast, UVB-treated monocytes induced normal proliferation and IL-4 production in Th2 cells. Stimulation of Th0 cell proliferation by UVB-irradiated monocytes was normal, but a preferential suppression of IFN-gamma production was observed, thus leading to a more Th2-like cytokine response. The loss of Th1 proliferation upon stimulation with UVB-irradiated monocytes could be overcome by rIL-2; however, IFN-gamma production remained suppressed. IFN-gamma production could be completely restored by rIL-12, whereas the addition of IL-1 beta, TNF-alpha, or indomethacin had no such effect, nor did the addition of mAb to CD28, added to compensate for the reduced B7 expression of UVB-irradiated monocytes. Monocytes exposed to UVB radiation exhibited reduced expression of mRNA for the IL-1 2 subunits p35 and p40 and suppressed production of the IL-12 p70 protein. Our results thus indicate that UVB irradiation of APC selectively impairs Th1-like responses, a phenomenon caused by the UVB-induced suppression of monocyte IL-12 production.
Kremer
I B
IB
Department of Dermatology, Academic Medical Center, University of Amsterdam, The Netherlands.
Hilkens
C M
CM
Sylva-Steenland
R M
RM
Koomen
C W
CW
Kapsenberg
M L
ML
Bos
J D
JD
Teunissen
M B
MB
D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000528:radiation effects; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000528:radiation effects*; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000528:radiation effects*; D009000:Monocytes / Q000378:metabolism* / Q000528:radiation effects*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays
D016207:Cytokines; D007376:Interleukin-2; D018664:Interleukin-12; D007371:Interferon-gamma