Visualization of Va14i NKT cells in vivo

描述（由申请人提供）：概述V114i NKT细胞涉及与广泛疾病相关的免疫应答的调节，包括自身免疫、感染性疾病和癌症。它们的调节功能被认为是通过它们对免疫系统的其他细胞的作用来介导的，然而在免疫应答期间这些细胞之间在体内的假定相互作用的性质是完全未知的。V114i NKT细胞的原位行为代表了一个新的研究领域，由于缺乏独特跟踪这些细胞所需的工具，该领域已被极大地忽视。我们建议生成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细胞中标记的V114i NKT细胞的可视化。这种情况将尽可能接近野生型动物的“正常”库，并将允许在静息动物中研究V114i NKT细胞的原位行为。 自然杀伤T细胞（NKT细胞）在调节各种免疫反应中发挥重要作用。近年来，关于这些细胞如何发育、识别其抗原并影响免疫反应，已经取得了几项重大进展。然而，这种淋巴细胞群体在组织中的定位及其迁移行为仍然未被探索。这在很大程度上是由于缺乏直接在体内明确鉴定该细胞群的试剂和模型。拟议的研究旨在产生一种动物模型，该模型将允许直接在体内观察NKT细胞群。对NKT细胞在组织中的定位和运输的理解可能被用于改善人类健康的治疗用途。

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.