MECHANISMS OF UV-INDUCED IMMUNE SUPPRESSION

皮肤暴露于紫外线(UV)辐射抑制T细胞- 对皮肤中遇到的抗原的介导性免疫反应 高免疫原性皮肤癌在实验动物中的生长。 紫外线辐射的免疫抑制是由多种、复杂的和 相互作用的机制。最近的研究表明，这种抑制是 由DNA损伤引发，随后产生免疫抑制 细胞因子，皮肤抗原提呈细胞(APC)丢失，改变 剩余的APC的功能，以及诱导抗原特异性 抑制性T细胞。然而，这些APC的调节和相互作用， 诱导抗原特异性抑制性T细胞。然而， 这些APC和细胞因子通路的调节和相互作用尚不清楚 对于接触过敏(CHS)反应，似乎是不同的 皮肤中的过敏原和迟发性超敏反应 微生物。 我们最近的研究表明，库拉索芦荟的粗提物可以保护 CHS和DTH对紫外线辐射抑制的反应。因为芦荟 提取物为被取消的免疫反应提供广泛的保护 由联合国通过不同的机制，它可以作为一个中央控制点在 压制。或者，芦荟可能含有几种作用于CHS的药物 和DTH。此外，芦荟在化学上与 抗体、细胞因子或其他已被用来探测 紫外线辐射诱导的抑制途径，可能是通过一种 机制新颖(S)。 我们将通过让小鼠暴露在紫外线辐射和 探讨芦荟处理对芦荟产量的影响 细胞因子TNF-α、IL-10和IL-12在培养的角质形成细胞中的表达 而且是在皮肤上。我们将调查对CHS和DTH的保护 反应是由芦荟中不同的成分分别介导的。我们会 同时检测芦荟对APC功能的影响。 用CHS反应半抗原建立小鼠淋巴转移模型 异硫氰酸荧光素，以及对白色念珠菌的迟发型超敏反应。在……里面 此外，我们建议研究芦荟保存的能力 对紫外线诱发的皮肤癌具有免疫力。澄清两国之间的关系 皮肤肿瘤免疫的CHS和DTH模型可能允许设计 更有效地保护人类免受 皮肤癌的发展。

Epicutaneous exposer to ultraviolet (UV) radiation suppresses T cell- mediated immune responses to antigens encountered in the skin and permits the growth of highly immunogenic skin cancers in laboratory animals. Immune suppression by UV radiation is mediated by multiple, complex, and interacting mechanisms. Recent studies indicate the suppression is triggered by DNA damage followed by production of immunosuppressive cytokines, loss of antigen presenting cells (APC) from the skin, alteration of the functions of remaining APC, and induction of antigen-specific suppressor T cells. However, the regulation nd interaction of these APC, and induction of antigen-specific suppressor T cells. However, the regulation and interaction of these APC and cytokine pathways are unclear and appears to be different for contact hypersensitivity (CHS) reactions to allergens in skin and delayed type hypersensitivity (DTH) reactions to microorganisms. We have recently shown that crude extracts of Aloe barbadensis gel protects CHS and DTH responses against suppression by UV radiation. Because Aloe extract provides broad protection for immune responses that are abrogated by UN by different mechanisms, it may act as a central controlling point in suppression. Alternatively Aloe may contain several agents that act on CHS and DTH separately. Furthermore, Aloe is chemically distinct from antibodies, cytokines, or other agents that have been used to probe suppression pathway induced by UV radiation, and it may be acting by a novel mechanism(s). We will test these hypotheses by exposing mice to UV radiation and examining the effect of Aloe treatment on the production of the regulatory cytokines TNF-alpha, IL-10, and Il-12 in cultured keratinocyte cell liens and in skin. We will investigate whether protection of CHS and DTH responses is mediated separately by different components in Aloe. We will also examine the effect of Aloe on the function of APC from the draining lymph nodes using the murine model of CHS response to the hapten fluorescein isothiocyanate, and the DTH response to Candida albicans. In addition, we propose to investigate the ability of Aloe to preserve immunity to UV-induced skin cancers. Clarification of the relationship of the CHS and DTH models to cutaneous tumor immunity may permit the design of therapeutic agents that are more effective in protecting humans against the development of skin cancer.