ASSAY FOR HAPTEN SPECIFIC PRIMING OF T LYMPHOCYTES

描述：(改编自《调查者摘要》)过敏和 刺激性接触性皮炎(ACD和ICD)是常见的炎症性皮肤 皮肤表面暴露于某些特定环境后的状况 环境制剂(接触式致敏剂或半抗原)。缺乏明确性 到目前为止，对ACD免疫发病机制的了解仍然是主要的 阻碍治愈或预防这些疾病。努力 对ACD的预防包括确定环境因素 会导致接触性超敏反应(CH)以及个体 容易受到这样的反应的影响。尽管众所周知，某些人 通用接触增敏剂是化学反应的低分子物质 重量的化合物，可以在接触时衍生蛋白质，并成为 免疫原性，目前尚不清楚为什么一些接触性致敏剂不能诱发CH 在所有的个体中。此外，目前可用于 接触性过敏原的鉴定不能区分过敏原 还有刺激物。用于鉴定接触性致敏剂的体外试验 FAR只取得了有限的成功。这些化验结果依赖于 T细胞的增殖反应，这是 炎症以外的一种CH反应。然而，T细胞的增殖已经 仍然是区分半抗原和 刺激物。基于半抗原AS独特的致敏特性 与刺激物相比，我们建议开发一种体外试验，这可能有助于 确定潜在的接触敏感者和刺激物以及个人 易患ACD或ICD。到目前为止，我们成功地 证明了产生半抗原特异性致敏T细胞的可能性 自体幼稚T细胞暴露于 半抗原衍生化培养的PBMC 5天。为了生成 致敏的T细胞与我们现在计划在体内发现的非常相似 比较体内和体外启动的T细胞的效应功能。这些 比较将包括T细胞的表型在一个 半抗原特异性方式、细胞因子谱和半抗原特异性 细胞毒性。将尝试比较和对比T细胞 对各种半抗原和刺激物的反应。因此，这个项目可以帮助(A) 完善一种可用于临床实验室的体外检测方法 筛选各种潜在的半抗原和刺激物以及易感物质 个人和(B)提供对细胞事件的更好理解 导致过敏性和刺激性接触性皮炎。

DESCRIPTION: (Adapted from the Investigator's Abstract) Allergic and irritant contact dermatitis (ACD and ICD) are common inflammatory skin conditions that result after exposure of the cutaneous surface to certain environmental agents (contact sensitizers or haptens). Lack of clear understanding of immunopathogenesis of ACD so far has remained the major hindrance in achieving cure or prevention of these disorders. Effort towards prevention of ACD include identification of environmental agents that induce contact hypersensitivity (CH) response as well as individuals that are susceptible for such a response. Although it is known that certain universal contact sensitizing agents are chemically reactive low molecular weight compounds that can derivatize proteins upon contact and become immunogenic, it is not known why some contact sensitizers do not induce CH in all the individuals. Also, currently available means for the identification of contact allergens can not discriminate between allergens and irritants. In vitro assays designed to identify contact sensitizers so far have met with limited success. These assays have relied on the proliferative responses of T cells, which is a predominant characteristic of a CH response besides inflammation. However, T cell proliferation has remained an inconsistent indicator for distinguishing haptens from irritants. Based on the distinct sensitizing properties of haptens as compared to irritants we propose to develop an in vitro assay that may help identify potential contact sensitizers and irritants as well as individuals susceptible to developing ACD or ICD. We have so far successfully demonstrated the possibility of generating hapten-specific sensitized T cells in vitro cultures in which autologous naive T cells are exposed to hapten derivatized cultured PBMC for 5 days. In order to generate sensitized T cells that closely resemble those found in vivo we now plan to compare effector functions of T cells primed in vivo and in vitro. These comparisons will include phenotype of the T cells proliferating in a hapten-specific manner, their cytokine profile and hapten-specific cytotoxicity. Attempts will be made to compare and contrast T cell responses to various haptens and irritants. Thus, this project can help (a) refine an in vitro assay for future application in clinical laboratory for screening various potential haptens and irritants as well as susceptible individuals and (b) provide better understanding of cellular events that lead to allergic versus irritant contact dermatitis.