Yoshikawa T, Kurimoto I, Streilein J W
Department of Microbiology and Immunology, University of Miami School of Medicine, Florida 33101.
Immunology. 1992 Jun;76(2):264-71.
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.
急性低剂量紫外线B辐射（UVB）会损害某些近交系小鼠（称为UVB敏感型）对二硝基氯苯（DNCB）的接触性超敏反应（CH）的诱导，但对其他小鼠（称为UVB抗性型）则无此影响。相比之下，有报道称将小鼠耳部皮肤暴露于相同的UVB照射方案下会加剧CH的表达。最近，已证明肿瘤坏死因子-α（TNF-α）介导UVB对CH诱导的有害作用，可能是通过在UVB照射的皮肤内局部释放TNF-α来实现的。进行本研究以确定TNF-α是否也介导UVB辐射诱导的CH的加剧表达。结果发现，在耳部激发部位皮内注射TNF-α可增强常规致敏小鼠对二硝基氟苯（DNFB）的CH表达。有趣的是，TNF-α能够增强UVB敏感型小鼠品系和UVB抗性型小鼠品系耳部的CH表达。然而，抗TNF-α抗体可中和UVB敏感型小鼠中UVB增强的CH，但对UVB抗性型小鼠则无此作用。这些发现支持以下观点：从UVB照射的表皮细胞释放的TNF-α是UVB辐射对接触性超敏反应诱导和表达影响的关键介质。还评估并比较了UVB辐射、皮内（ID）TNF-α和/或经皮应用DNFB对表皮朗格汉斯细胞的影响。单独经皮应用DNFB会使表皮中的朗格汉斯细胞大量减少，而涂抹在UVB照射或TNF-α处理过的皮肤上的DNFB在消除外观正常的朗格汉斯细胞方面效果要差得多。这些结果表明，TNF-α对朗格汉斯细胞的一个直接作用可能是将这些抗原呈递细胞暂时固定在表皮内。有人提出，这种固定作用具有矛盾的效果：（a）通过阻止携带半抗原 的朗格汉斯细胞迁移至引流淋巴结来干扰致敏，而同时（b）通过延长半抗原在表皮中的保留和呈递时间间隔来增强CH表达。
