ULTRASTRUCTURAL STUDIES BEARING ON THE MECHANISM OF UVB-IMPAIRED INDUCTION OF CONTACT HYPERSENSITIVITY TO DNCB IN MAN

In both murine and human experimental systems, acute, low dose exposur e of skin to ultraviolet B light (UVB) impairs the induction of allerg ic contact dermatitis (ACD) by haptens such as dinitrochlorobenzene (D NCB) in a significant proportion of individuals. By light microscopy, epidermal Langerhans cells (LC) have been reported to be depleted by U VB exposure as well as by epicutaneous hapten application, implying th at LC may be the locus of action of the effects of both UVB and DNCB. However, light microscopy can not readily distinguish cell density cha nges secondary to LC necrosis from changes resulting from down-modulat ion of expression of LC surface molecules. Using a highly sensitive im munogold electron microscopic approach, we have evaluated the differen tial effects of UVB and/or DNCB on human epidermal LC. The results rev eal that DNCB alone caused significant up-regulation of cell surface H LA class II expression on a very small number of LC, the major fractio n of LC expressing normal levels of HLA class II. Furthermore, DNCB al one caused a modest reduction in the density of LC at the treated site s without evidence of cell necrosis. Treatment with UVB alone or UVB e xposure followed by DNCB resulted in a reduction in the density of LC, with widespread evidence of LC necrosis. However, the few remaining i ntact LC were all intensely HLA class II-positive after UVB exposure f ollowed by DNCB, whereas treatment with UVB alone did not result in ch anges in LC HLA class II expression. The findings that after DNCB pain ting only a small proportion of the LC were strongly HLA class II-posi tive, but after UVB exposure followed by DNCB all intact LC displayed significant up-regulation of cell surface HLA class II expression, imp ly that UVB exposure inhibits the migration of epidermal LC. This is c onsistent with the view that DNCB fails to induce ACD when hapten is p ainted on UVB-exposed skin because insufficient LC are available to in itiate T cell activation in the draining lymph node.