EFFECTS OF ASBESTOS ON T CELL ACTIVATION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 除草剂6-氯-N-乙基-N '-（1-甲基乙基）-三嗪-2，4-二胺（莠去津; ATR）是美国最频繁施用的除草剂之一。 美国环保署估计，美国多达70%的地下水受到ATR污染。它是一种雌激素干扰化学物质，与生殖异常有关，包括低出生体重、早产和胎盘变薄，以及发育中胎儿的心脏、泌尿系统和肢体缺陷。一些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可能是免疫抑制，而其他人认为，它可能会提高免疫状态的污染个人。 为了解决ATR对免疫功能的影响，并解决这些相互矛盾的数据，该提案侧重于CD 4 + T辅助细胞的活化和分化，这是产生适应性免疫应答的关键事件。CD 4 + T细胞为B细胞提供细胞因子和接触依赖性帮助，促进免疫球蛋白分泌并允许同种型转换。CD 4 + T细胞还涉及通过抗原呈递细胞的活化或“许可”产生保护性细胞免疫应答。在本提案中，我们将研究两个具体目标，以评估ATR暴露对CD 4 + T细胞活化的影响：目标1。研究阿特拉津对抗原呈递、免疫突触形成和随后的T细胞活化的影响;目的2.确定阿特拉津对CD 4 + T细胞分化偏斜的影响。

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.