IRRITANTS EFFECTS ON EPIDERMAL ANTIGEN PRESENTATION

描述：(改编自《调查者摘要》)刺激性接触 皮炎(ICD)是一种常见且临床重要的炎症性疾病。 皮肤病，被认为是非免疫性的结果 由于皮肤的化学损伤而引起的炎症。这是在 与过敏性接触性皮炎(ACD)不同，ACD是半抗原特异性CD4+ T淋巴细胞被认为在该病的免疫发病机制中起关键作用。 皮炎的类型。然而，以前的临床、组织学和免疫学 比较刺激性和过敏性接触性皮炎的研究表明 在大多数化验中，这两种皮炎即使不是相似的，也是相似的 一模一样。我们假设刺激性和过敏性接触性皮炎 共同的免疫介导的皮肤损伤的共同途径，导致 两种接触性皮炎的常见表型。刺激物和 过敏原破坏表皮，导致自身抗原的释放。 我们假设这些自身抗原被提呈给自身反应。 由表皮抗原提呈细胞(APC)介导的T淋巴细胞，APC是 刺激性和过敏性接触性皮炎的发病机制。至 检验我们的假设，我们将研究刺激物对人类的直接影响 角质形成细胞(KC)和朗格汉斯细胞(LC)样树突状细胞(DC) 它们表达的黏附分子和细胞因子是已知的 对调节APC功能或T淋巴细胞生长至关重要。抗原 正常或刺激处理的表皮KC或LC样树突状细胞的呈递 将对皮肤归巢T淋巴细胞亚群进行研究。自体的 混合淋巴细胞反应将被用来呈现模型 刺激性应激表皮对自身反应性T淋巴细胞的自身抗原作用 APC。将对以下T淋巴细胞群体进行研究 针对刺激性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； 渗入刺激性皮肤刺激部位的T淋巴细胞；或 衍生的非经典T淋巴细胞(CD4-CD8-，T细胞受体y/8) 取自正常人的表皮。这些研究将定义新的免疫学 ICD的机制，并将有助于更好地理解 刺激物对APC功能的调节及随后的相互作用 有皮肤归巢的T淋巴细胞。这些分析中的一些可能是有用的 体外实验，以确定易激惹的个体。由于ICD可以是一种 可能影响数百万美国人的衰弱皮肤问题， 用体外试验鉴定易受刺激的个体 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.