Contact hypersensitivity (CHS) response is clinically known as allergic contact dermatitis, which affects about 5% of men and 11% of women in industrialized countries and is one of the leading causes of occupational diseases. CHS is a classical example of an adaptive immune response, in which T cells and B-1 B cells have been shown to play a role. Natural Killer (NK) cells had been generally believed to mediate only innate immune responses. However, the von Andrian laboratory reported new observations indicating that NK cells can also mediate CHS as an antigen (Ag)-specific, long lasting adaptive response in mice independent of B and T cells. Adoptive transfer experiments showed that only hepatic NK cells are capable of causing this CHS response. In this project, we propose to investigate the trafficking of hepatic NK cells and their education by antigen presenting cells (APC). Specifically, we plan to understand where and how NK cells learn to recognize hapten-based Ag to induce a specific CHS response. Moreover, we will examine whether regulatory T (Treg) cells can modulate the activity of NK cells during the NK-mediated CHS response. Some evidence in the literature indicates that Treg cells do play a role during αβ T cell-mediated CHS by mechanisms that are still unclear. Whether Treg cells also play a role during NK cell-mediated CHS is unknown. The von Andrian laboratory has established state-of-the-art multiphoton microscopy technology and extensive expertise in intravital imaging, which will allow us to study cell trafficking in anesthetized animals. Using transgenic mice and adoptive transfer of fluorescently labeled leukocyte subsets, we will study in vivo the cross talk between APC and NK cells and between Treg and NK cells during the priming and effector phase of CHS. This project will contribute to our understanding of how adaptive and innate immunity is coordinated, thereby potentially allowing the development of novel approaches to immunotherapy.
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