Garssen J, Vandebriel R J, De Gruijl F R, Wolvers D A, Van Dijk M, Fluitman A, Van Loveren H
Laboratory for Pathology and Immunobiology, National Institute of Public Health and The Environment, Bilthoven, the Netherlands.
Immunology. 1999 Jul;97(3):506-14. doi: 10.1046/j.1365-2567.1999.00801.x.
Exposure to ultraviolet light, especially UVB wavelengths, can impair immune responses in animals and humans. It is remarkable that this immunomodulation is not restricted to the exposed skin but is also found at other sites, i.e. systemic (distant) immunosuppression. A frequently proposed hypothesis is that UVB exposure inhibits, specifically, T helper 1 (Th1)-mediated immune responses. The major reason for this is that contact hypersensitivity (CHS) and delayed-type hypersensitivity (DTH), both Th1-mediated immune responses, are very sensitive to UVB. For this reason these models are frequently used for photoimmunology studies. In the present study, the effects of UVB exposure were investigated in classical models for Th1-mediated immunity, i.e. CHS models in which picrylchloride or oxazolone were used as low-molecular-weight chemical antigens. In these models, CHS responsiveness and cytokines were measured, the latter by both reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The CHS responses to both contact sensitizers (picrylchloride and oxazolone) were suppressed significantly by pre-exposure to repeated suberythemal UVB exposure. Interferon-gamma (IFN-gamma), interleukin (IL)-12 and IL-4, but not IL-10, were detectable in spleen and draining lymph nodes of sensitized BALB/c mice. Repeated UVB exposure prior to sensitization at a distant locus inhibited both IFN-gamma and IL-12 but not IL-4. In BALB/c mice sensitized with ovalbumin (OVA) in the absence of complete Freund's adjuvant, a model for Th2-mediated immunity, OVA-specific serum IgE and cytokine profiles in the spleen were analysed. Sensitization did lead to a significant increase in OVA-specific IgE serum titres. Pre-exposure to UVB resulted in a decreased OVA-specific IgE serum titre. Both RT-PCR and ELISA showed increased levels of IFN-gamma, IL-4 and IL-10 in the spleens of OVA-sensitized mice. The production of IFN-gamma and IL-4 was not affected by UVB pre-exposure. In contrast, the production of IL-10 was significantly increased. This was probably caused by an up-regulation of Th2 cells. It is remarkable that IFN-gamma is significantly suppressed by UVB in Th1-mediated immune reactions but not in Th2-mediated immune reactions where it even appears to increase. IL-10, which is up-regulated by UVB pre-exposure and produced by, among others, Th2 cells, may represent a shift from Th1- to Th2-mediated immune mechanisms. However, IL-10 can also inhibit Th2 responses, which might be the reason for a decreased IgE titre in the Th2 model. From the results of this study it is concluded that UVB exposure prior to sensitization/immunization not only inhibits Th1-mediated but also Th2-mediated immune responses.
暴露于紫外线，尤其是中波紫外线（UVB）波长，会损害动物和人类的免疫反应。值得注意的是，这种免疫调节不仅限于暴露的皮肤，在其他部位也会出现，即全身性（远处）免疫抑制。一个经常被提出的假说是，UVB暴露会特异性抑制辅助性T细胞1（Th1）介导的免疫反应。主要原因是，接触性超敏反应（CHS）和迟发型超敏反应（DTH），这两种都是Th1介导的免疫反应，对UVB非常敏感。因此，这些模型经常用于光免疫学研究。在本研究中，在Th1介导免疫的经典模型中研究了UVB暴露的影响，即使用苦味酸氯或恶唑酮作为低分子量化学抗原的CHS模型。在这些模型中，测量了CHS反应性和细胞因子，后者通过逆转录-聚合酶链反应（RT-PCR）和酶联免疫吸附测定（ELISA）进行检测。预先暴露于重复的亚红斑量UVB照射可显著抑制对两种接触致敏剂（苦味酸氯和恶唑酮）的CHS反应。在致敏的BALB/c小鼠的脾脏和引流淋巴结中可检测到干扰素-γ（IFN-γ）、白细胞介素（IL）-12和IL-4，但未检测到IL-10。在远处位点致敏前重复UVB照射可抑制IFN-γ和IL-12，但不抑制IL-4。在没有完全弗氏佐剂的情况下用卵清蛋白（OVA）致敏的BALB/c小鼠中，这是一个Th2介导免疫的模型，分析了脾脏中OVA特异性血清IgE和细胞因子谱。致敏确实导致OVA特异性IgE血清滴度显著增加。预先暴露于UVB导致OVA特异性IgE血清滴度降低。RT-PCR和ELISA均显示OVA致敏小鼠脾脏中IFN-γ、IL-4和IL-10水平升高。UVB预先暴露不影响IFN-γ和IL-4的产生。相反，IL-10的产生显著增加。这可能是由Th2细胞的上调引起的。值得注意的是，在Th1介导的免疫反应中UVB可显著抑制IFN-γ，但在Th2介导的免疫反应中则不然，在Th2介导的免疫反应中IFN-γ甚至似乎增加。UVB预先暴露上调并由Th2细胞等产生的IL-10可能代表从Th1介导的免疫机制向Th2介导的免疫机制的转变。然而，IL-10也可抑制Th2反应，这可能是Th2模型中IgE滴度降低的原因。从本研究结果得出结论，致敏/免疫前暴露于UVB不仅抑制Th1介导的免疫反应，也抑制Th2介导的免疫反应。
