EFFECTS OF ASBESTOS ON T CELL ACTIVATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 除草剂阿特拉津(6-chloro-N-ethyl-N‘-(1-methylethyl)-triazine-2，4-diamine)是美国应用最广泛的除草剂之一。美国环保局估计，美国多达70%的地下水受到ATR的污染。它是一种雌激素干扰性化学物质，与生育异常有关，包括低出生体重、早产和胎盘变薄，以及发育中胎儿的心脏、尿路和四肢缺陷。有几份报告表明与前列腺癌、乳腺癌和淋巴癌有关，但这种联系仍然存在争议。ATR的免疫毒性潜力目前也不清楚。一些报告表明，急性暴露于ATR可能会抑制免疫，而另一些报告则表明，它可能会提高受污染个人的免疫状态。为了解决ATR对免疫功能的影响和解决这些相互矛盾的数据，这项建议侧重于CD4+T辅助细胞的激活和分化，这是产生适应性免疫反应的关键事件。CD4+T细胞为B细胞提供细胞因子和接触性帮助，促进免疫球蛋白分泌，并允许同型转换。通过激活或“许可”抗原提呈细胞，CD4+T细胞也参与了保护性细胞免疫反应的产生。在这项建议中，我们将检查两个特定的目的，以评估ATR暴露对CD4+T细胞激活的影响：目的1.检测阿特拉津对抗原提呈、免疫突触形成和随后的T细胞激活的影响；目的2.确定阿特拉津对CD4+T细胞分化的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The herbicide 6-chloro-N-ethyl-N'-(1-methylethyl)-triazine-2,4-diamine (Atrazine; ATR) is among the most heavily applied herbicides in the US. The US EPA has estimated that as much as 70% of all ground water in the US is contaminated by ATR. It is an estrogen disrupting chemical that has been associated with reproductive abnormalities including low birth weight, premature birth and placental thinning, as well as heart, urinary and limb defects in the developing fetus. Several reports have suggested a link to prostate, breast and lymphatic cancers, but this link remains controversial. The immunotoxic potential of ATR is also currently unclear. Several reports suggest that acute exposure to ATR may be immunosuppressive, while others suggest that it may enhance immune status in contaminated individuals. To address the effects of ATR on immune function and resolve these conflicting data, this proposal focuses on the activation and differentiation of CD4+ T helper cells, a key event in the generation of an adaptive immune response. CD4+ T cells provide cytokine and contact-dependent help to B cells boosting immunoglobulin secretion and allowing for isotype switching. CD4+ T cells are also implicated in the generation of protective cellular immune responses via the activation or "licensing" of antigen presenting cells. In this proposal we will examine two specific aims to assess the impact that ATR exposure has on CD4+ T cell activation: Aim 1. Examine the effect of atrazine on antigen presentation, immunological synapse formation and subsequent T cell activation; Aim 2. Determine effects of Atrazine on the skewing of CD4+ T cell differentiation.