Visualization of Va14i NKT cells in vivo

描述(申请人提供)：V114i NKT细胞参与调节与多种疾病相关的免疫反应，包括自身免疫、传染病和癌症。它们的调节功能被认为是通过它们对免疫系统中其他细胞的作用来实现的，然而这些细胞在体内免疫反应过程中可能相互作用的性质完全未知。V114i NKT细胞的原位行为代表了一个新的研究领域，由于缺乏唯一追踪这些细胞的必要工具，该领域已被广泛忽视。我们建议建立一种新的转基因小鼠模型，该模型将允许在未标记的“常规”T细胞中显示标记的V114i NKT细胞。这种情况将尽可能地概括野生动物的“正常”曲目，并将允许研究V114i NKT细胞在静息动物中的原位行为。 与公共健康相关的自然杀伤T细胞(Natural Killer T cell，NKT细胞)在调节多种免疫反应中发挥着重要作用。近年来，在这些细胞如何发育、识别其抗原和影响免疫反应方面取得了一些重大进展。然而，这种淋巴细胞群体在组织中的定位及其迁移行为仍未被探索。这在很大程度上是因为缺乏试剂和模型来直接在体内明确地识别这一细胞群体。拟议的研究旨在建立一种动物模型，使NKT细胞群体能够直接在体内可视化。了解NKT细胞在组织中的定位和贩运可能被用于治疗，以改善人类健康。

DESCRIPTION (provided by applicant): Summary V114i NKT cells have been implicated in the regulation of immune responses associated with a broad range of diseases, including autoimmunity, infectious diseases and cancer. Their regulatory functions are thought to be mediated by their action on other cells of the immune system, yet the nature of the putative interactions among these cells in vivo during the immune response is totally unknown. V114i NKT cells behavior in situ represents a new area of investigation that has been vastly ignored because of the lack of tools necessary to uniquely track these cells. We propose to generate a new transgenic mouse model that will allow for the visualization of labeled-V114i NKT cells among unlabeled "conventional" T cells. This situation will recapitulate as closely as possible the "normal" repertoire of wild-type animals and will permit the study of the in situ behavior of V114i NKT cells in resting animals. PUBLIC HEALTH RELEVANCE Natural Killer T cells (NKT cells) play an important role in regulating a variety of immune responses. Several major advances have been made in the recent years regarding how these cells develop, recognize their antigens and influence immune responses. Yet, the localization of this lymphocyte population in tissues and its migratory behavior remains unexplored. This is largely due to the lack of reagents and models to unambiguously identify this cell population directly in vivo. The proposed studies aim at producing an animal model that will allow for the visualization of the NKT cell population directly in vivo. An understanding of NKT cell localization and trafficking in tissues could potentially be exploited for therapeutic usage to improve human health.