Shimizu T, Streilein J W
Department of Microbiology and Immunology, University of Miami School of Medicine, Florida.
Immunology. 1994 May;82(1):140-8.
Tumour necrosis factor-alpha (TNF-alpha) and cis-urocanic acid (UCA) have recently been implicated in the process by which ultraviolet B radiation (UVB) impairs the induction of contact hypersensitivity when dinitrofluorobenzene (DNFB) is painted on UVB-exposed skin. The evidence supports the hypothesis that UVB radiation converts trans- to cis-UCA in the epidermis which in turn causes the epidermis of UVB-susceptible mice to produce/contain excessive local amounts of TNF-alpha. When hapten is painted on TNF-alpha- or UVB-treated skin, contact hypersensitivity fails to develop. As UVB radiation also induces hapten-specific tolerance and suppressor T cells when hapten is applied to UVB-exposed skin of UVB-susceptible strains of mice, we examined whether TNF-alpha and/or UVB-irradiated UCA (UV-UCA) might be similarly involved in the mechanism by which UVB induces tolerance. We report that intracutaneously-injected TNF-alpha and UV-UCA altered the cutaneous environment such that when DNFB was painted on the injected site, hapten-specific tolerance was induced and suppressor cells were generated. However, the tolerance induced by UVB radiation and the tolerance that followed intracutaneous injection of UV-UCA were not reversed by neutralizing anti-TNF-alpha antibodies. Moreover, UV-UCA and TNF-alpha-induced tolerance and suppressor cells in both UVB-susceptible (UVB-S) and UVB-resistant mice, whereas UVB radiation induced tolerance only in UVB-S mice. We conclude that the mechanism by which UVB radiation induces tolerance in mice is separate and distinct from the mechanism by which UVB radiation impairs contact hypersensitivity induction. Moreover, our data support the view that the generation of suppressor cells and the development of hapten-specific tolerance may be mechanistically distinct. The possible molecular and cellular mediators of UVB-induced tolerance are discussed.
肿瘤坏死因子-α（TNF-α）和顺式尿刊酸（UCA）最近被认为参与了以下过程：当在紫外线B（UVB）照射过的皮肤上涂抹二硝基氟苯（DNFB）时，UVB会损害接触性超敏反应的诱导。有证据支持这样的假说：UVB辐射在表皮中将反式UCA转化为顺式UCA，这反过来又导致UVB敏感小鼠的表皮产生/含有过量的局部TNF-α。当在TNF-α或UVB处理过的皮肤上涂抹半抗原时，接触性超敏反应无法发生。由于当半抗原应用于UVB敏感品系小鼠的UVB照射皮肤时，UVB辐射也会诱导半抗原特异性耐受和抑制性T细胞，我们研究了TNF-α和/或UVB照射的UCA（UV-UCA）是否同样参与UVB诱导耐受的机制。我们报告，皮内注射TNF-α和UV-UCA改变了皮肤环境，使得当在注射部位涂抹DNFB时，会诱导半抗原特异性耐受并产生抑制性细胞。然而，UVB辐射诱导的耐受以及皮内注射UV-UCA后产生的耐受，不会被中和性抗TNF-α抗体逆转。此外，UV-UCA和TNF-α在UVB敏感（UVB-S）和UVB抗性小鼠中均诱导耐受和抑制性细胞，而UVB辐射仅在UVB-S小鼠中诱导耐受。我们得出结论，UVB辐射在小鼠中诱导耐受的机制与UVB辐射损害接触性超敏反应诱导的机制是分开且不同的。此外，我们的数据支持这样的观点，即抑制性细胞的产生和半抗原特异性耐受的形成在机制上可能是不同的。本文还讨论了UVB诱导耐受的可能分子和细胞介质。
