Ultrastructural studies bearing on the mechanism of UVB-impaired induction of contact hypersensitivity to DNCB in man

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Abstract
In both murine and human experimental systems, acute, low dose exposure of skin to ultraviolet B light (UVB) impairs the induction of allergic contact dermatitis (ACD) by haptens such as dinitrochlorobenzene (DNCB) in a significant proportion of individuals. By light microscopy, epidermal Langerhans cells (LC) have been reported to be depleted by UVB exposure as well as by epicutaneous hapten application, implying that LC may be the locus of action of the effects of both UVB and DNCB. However, light microscopy can not readily distinguish cell density changes secondary to LC necrosis from changes resulting from down-modulation of expression of LC surface molecules. Using a highly sensitive immunogold electron microscopic approach, we have evaluated the differential effects of UVB and/or DNCB on human epidermal LC. The results reveal that DNCB alone caused significant up-regulation of cell surface HLA class II expression on a very small number of LC, the major fraction of LC expressing normal levels of HLA class II. Furthermore, DNCB alone caused a modest reduction in the density of LC at the treated sites without evidence of cell necrosis. Treatment with UVB alone or UVB exposure followed by DNCB resulted in a reduction in the density of LC, with widespread evidence of LC necrosis. However, the few remaining intact LC were all intensely HLA class II-positive after UVB exposure followed by DNCB, whereas treatment with UVB alone did not result in changes in LC HLA class II expression. The findings that after DNCB painting only a small proportion of the LC were strongly HLA class II-positive, but after UVB exposure followed by DNCB all intact LC displayed significant up-regulation of cell surface HLA class II expression, imply that UVB exposure inhibits the migration of epidermal LC. This is consistent with the view that DNCB fails to induce ACD when hapten is painted on UVB-exposed skin because insufficient LC are available to initiate T cell activation in the draining lymph node.