Tumour necrosis factor-alpha mediates ultraviolet light B-enhanced expression of contact hypersensitivity.
Acute, low-dose ultraviolet B radiation (UVB) impairs the induction of contact hypersensitivity (CH) to dinitrochlorobenzene (DNCB) in certain inbred strains of mice (termed UVB-susceptible), but not in others (termed UVB-resistant). By contrast, exposure of mouse ear skin to an identical regimen of UVB has been reported to exaggerate the expression of CH. Recently, tumour necrosis factor-alpha (TNF-alpha) has been demonstrated to mediate the deleterious effects of UVB on CH induction, presumably through local release of TNF-alpha within UVB exposed skin. The present studies were conducted to determine whether TNF-alpha also mediates the exaggerated expression of CH induced by UVB radiation. It was found that TNF-alpha, injected intradermally at the ear challenge site, enhanced the expression of CH to DNFB in conventionally sensitized mice. Interestingly, TNF-alpha was able to amplify the expression of CH in the ears of both UVB-susceptible strains of mice, and UVB-resistant strains. However, anti-TNF-alpha antibodies neutralized UVB-enhanced CH in UVB-susceptible mice, but not in UVB-resistant mice. These findings support the proposition that TNF-alpha, released from UVB-exposed epidermal cells, is a critical mediator of the effects of UVB radiation on induction and expression of contact hypersensitivity. The effects of UVB radiation, intradermal (ID) TNF-alpha, and/or epicutaneously applied DNFB on epidermal Langerhans' cells were also evaluated and compared. Whereas epicutaneously applied DNFB alone profoundly depleted the epidermis of Langerhans' cells, DNFB painted on UVB-exposed or TNF-alpha-treated skin was much less effective at eliminating normal appearing Langerhans' cells. These results suggest that one direct effect of TNF-alpha on Langerhans' cells may be to immobilize these antigen-presenting cells transiently within the epidermis. It is proposed that this immobilization has the paradoxical effect (a) of interfering with sensitization, by preventing hapten-bearing Langerhans' cells from migrating to the draining lymph node, while at the same time (b) of amplifying CH expression by lengthening the interval of hapten retention and presentation with the epidermis.
Yoshikawa
T
T
Department of Microbiology and Immunology, University of Miami School of Medicine, Florida 33101.
Kurimoto
I
I
Streilein
J W
JW
D000818:Animals; D000906:Antibodies / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology*; D004139:Dinitrofluorobenzene / Q000276:immunology; D004817:Epidermis / Q000528:radiation effects; D005260:Female; D007801:Langerhans Cells / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D014466:Ultraviolet Rays
D000906:Antibodies; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004139:Dinitrofluorobenzene