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.
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