EFFECTS OF ASBESTOS ON T CELL ACTIVATION

石棉对 T 细胞激活的影响

• 批准号: 8167596
• 负责人: SCOTT Allen WETZEL
• 金额: $ 15.56万
• 依托单位: UNIVERSITY OF MONTANA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167596
• 关键词: Acute; Address; Antigen Presentation; Antigen-Presenting Cells; Asbestos; Atrazine; B-Lymphocytes; Breast; CD4 Positive T Lymphocytes; Cells; Chemicals; Computer Retrieval of Information on Scientific Projects Database; Conflict (Psychology); Data; Defect; Diamines; Estrogens; Event; Exposure to; Fetus; Funding; Generations; Grant; Heart; Helper-Inducer T-Lymphocyte; Herbicides; Immune; Immune response; Immunoglobulin Class Switching; Immunoglobulins; Immunosuppressive Agents; Individual; Institution; Licensing; Limb structure; Link; Low Birth Weight Infant; Premature Birth; Prostate; Reporting; Research; Research Personnel; Resources; Source; T cell differentiation; T-Cell Activation; Triazines; United States National Institutes of Health; cytokine; ground water; immune function; immunological synapse formation; lymphatic cancer; reproductive; urinary

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 除草剂6-氯-N-乙基-N' - （1-甲基乙基） - 三嗪-2,4-二胺（Atrazine; ATR）是美国最重的除草剂之一。 美国EPA估计，美国所有地下水中多达70％的地下水受到ATR污染。这是一种雌激素破坏化学物质，与生殖异常有关，包括低出生体重，早产和胎盘稀疏，以及发育中的胎儿中的心脏，尿和肢体缺陷。几份报告提出了与前列腺，乳腺癌和淋巴癌的联系，但这种联系仍然有争议。目前尚不清楚ATR的免疫毒性潜力。几份报告表明，急性暴露于ATR可能是免疫抑制的，而另一些报告可能会增强受污染个体的免疫状态。 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，该建议着重于CD4+ T辅助细胞的激活和分化，这是生成适应性免疫反应的关键事件。 CD4+ T细胞为B细胞提供了细胞因子和接触依赖性的帮助，从而增强免疫球蛋白分泌并允许同型切换。 CD4+ T细胞还与抗原呈递细胞的激活或“许可”有关保护性细胞免疫反应的产生。在该提案中，我们将研究两个具体的目的，以评估ATR暴露对CD4+ T细胞激活的影响：AIM 1。检查阿特拉津对抗原表现，免疫突触形成以及随后的T细胞激活的影响； AIM 2。确定阿特拉津对CD4+ T细胞分化偏斜的影响。