IRRITANTS EFFECTS ON EPIDERMAL ANTIGEN PRESENTATION

描述：（改编自研究者摘要）刺激性接触 皮炎（ICD）是一种常见的和临床上重要的炎性类型， 皮肤病，并被认为是非免疫性的结果， 由于化学物质对皮肤的伤害而引起的炎症。 这是 与过敏性接触性皮炎（ACD）相反，在ACD中，半抗原特异性CD 4 + T淋巴细胞被认为是关键的免疫发病机制， 皮炎类型。 然而，先前的临床、组织学和免疫学检查 比较刺激性和过敏性接触性皮炎的研究表明， 在大多数试验中，这两种类型的皮炎是相似的，如果不是， 一模一样 我们假设刺激性和过敏性接触性皮炎 共享免疫介导的皮肤损伤的共同途径，导致 两种接触性皮炎的共同表型。 刺激物和 过敏原损伤表皮，导致自身抗原的释放。 我们假设这些自身抗原被呈递给自身反应性的 T淋巴细胞通过表皮抗原呈递细胞（APC），这是中央 刺激性和过敏性接触性皮炎的发病机制。 到 为了验证我们的假设，我们将研究刺激物对人体的直接影响。 角质形成细胞（KC）和朗格汉斯细胞（LC）样树突状细胞（DC）， 它们的粘附分子和细胞因子的表达是已知的， 对调节APC功能或T淋巴细胞生长至关重要。 抗原 通过正常或刺激物处理的表皮KC或LC样DC细胞呈递 将研究皮肤归巢T淋巴细胞群。 自体 将使用混合淋巴细胞反应模型来呈现 刺激应激表皮细胞对自身反应性T淋巴细胞的自身抗原 装甲运兵车 将研究以下T淋巴细胞群， 对刺激物处理的APC的自身反应性：皮肤归巢T细胞群 （皮肤白细胞抗原+）（CLA）来源于外周血; T淋巴细胞浸润到刺激性皮肤激发部位;或 非经典T淋巴细胞（CD 4-CD 8-，T细胞受体γ/8）来源 从正常人的表皮中分离出来 这些研究将定义新的免疫学 ICD的机制，并将导致更好地了解的影响， 刺激物对APC功能的调节及随后的相互作用 皮肤归巢T淋巴细胞 这些测定中的一些可用作免疫测定。 体外识别有刺激性风险的个体。 由于ICD可以是 使人衰弱的皮肤问题，可能影响数百万美国人， 使用体外试验识别有刺激性风险的个体 将有助于防止这种常见的和潜在的禁用 条件

DESCRIPTION: (Adapted from the Investigator's Abstract) Irritant contact dermatitis (ICD) is a common and clinically important type of inflammatory skin disorder, and is thought to be the result of non-immunologic inflammation resulting from chemical injury to the skin. This is in contrast to allergic contact dermatitis (ACD), in which hapten specific CD4+ T-lymphocytes are thought to be critical in the immunopathogenesis of this type of dermatitis. However, previous clinical, histologic and immunologic research studies comparing irritant to allergic contact dermatitis indicated that in most assays, these two types of dermatitis are similar, if not identical. We hypothesize that irritant and allergic contact dermatitis share common pathways of immune-mediated skin damage, resulting in the common phenotype of the two kinds of contact dermatitis. Irritants and allergens damage the epidermis, resulting in the release of self-antigens. We hypothesize that these self-antigens are presented to auto-reactive T-lymphocytes by epidermal antigen presenting cells (APC), which are central to the pathogenesis of both irritant and allergic contact dermatitis. To test our hypothesis, we will study the direct effects of irritants on human keratinocytes (KC) and Langerhans cell (LC)-like dendritic cells (DC) in their expression of adhesion molecules and cytokines that are known to be critical for regulating APC-functions or T-lymphocyte growth. Antigen presentation by normal or irritant-treated epidermal KC or LC-like DC cells to skin homing T-lymphocyte populations will be studied. The autologous mixed lymphocyte reaction will be used a model for presentation of self-antigens to autoreactive T-lymphocytes by irritant-stressed epidermal APC. The following T-lymphocyte populations will be studied for autoreactivity against irritant-treated APC: Skin homing T-cell populations (Cutaneous leukocyte antigen+) (CLA) derived from the peripheral blood; T-lymphocytes that infiltrate into irritant skin challenge sites; or non-classical T-lymphocytes (CD4-CD8-, T-cell receptor y/8 bearing) derived from normal human epidermis. These studies will define novel immunologic mechanisms of ICD, and will lead to a better understanding of the effects of irritants on the regulation of APC function and the subsequent interactions with skin homing T-lymphocytes. Some of these assays may be useful as an in vitro to identify individuals at risk for irritancy. Since ICD can be a debilitating skin problem that potentially affects millions of Americans, the identification of individuals at risk for irritancy using in vitro tests would be of utility in preventing this common and potentially disabling condition.