S. Nakagawa et al., Differential modulation of human epidermal Langerhans cell maturation bg ultraviolet B radiation, J IMMUNOL, 163(10), 1999, pp. 5192-5200
UVB irradiation of the skin causes immunosuppression and Ag-specific tolera
nce in which Langerhans cells (LC) are involved. We tested the effect of UV
B on LC that had migrated out of cultured epidermal sheets derived from the
skin that was irradiated es vivo (200, 400, 800, or 1600 J/m(2)). Two sepa
rate subpopulations of LC were distinguished: large-sized LC with high HLA-
DR expression, and HLA-DR-low, small LC, UVB stimulated the maturation of t
he former LC subset as demonstrated by enhanced up-regulation of CD80, CD86
, CD54, CD40, and CD83 and reduced CD1a expression in comparison with unirr
adiated controls. In contrast, the latter LC exhibited little or no up-regu
lation of these molecules except for high CD1a expression and high binding
of annexin V, indicating that they were apoptotic, although their CD95 expr
ession was relatively low. Stimulation of enriched LC with CD40 ligand-tran
sfected cells and IFN-gamma revealed that the release of IL-1 beta, IL-6, I
L-8, and TNF-alpha was enhanced by UVB, In comparison with HLA-DR-low LC, H
LA-DR-high LC were the principal IL-8 producers as demonstrated by intracel
lular cytokine staining, and they retained more accessory function. There w
as no detectable secretion of IL-12 p70, and IL-18 production was neither a
ffected by any stimulus nor by UVB. These results suggest a dual action of
UVB on LC when irradiated in situ: 1) immunosuppression by preventing matur
ation and inducing apoptotic cell death in part of LC, and 2) immunopotenti
ation by enhancing the up-regulation of costimulatory molecules and the pro
duction of preinflammatory cytokines in another part.