REGULATION OF ACIAD BY LYMPHOCYTES WITH NK MARKERS

免疫学家几十年前就知道，免疫是细胞介导和抗体介导的各种反应的结果。近年来，由于T辅助细胞可以采用两种极性类型的反应性之一：T辅助1 （Th1）和T辅助2 (Th2)，从而进一步定义了可能的免疫反应的二分法。这些对抗反应可以通过细胞因子表型（Th1, IFNgamma; Th2, IL4, IL10）和抗体同型（Th1: IgG2a; Th2: IgG1, IgE）的差异来区分。Th1反应与炎症有关，而Th2反应与炎症有关，而Th2反应与超敏反应和防止寄生虫入侵有关。由于这两种极性反应相互交叉调节，Th2反应可能在包括眼睛在内的各种器官的炎症预防中起重要作用。显然，在健康的眼睛中，由于前房不寻常的局部调节机制，很难诱导Th1反应。这项研究计划将研究被称为前房相关免疫偏差（ACAID）的眼部调节机制。ACAID与Th2反应上调和Th1反应下调有关，即炎症，从而保持视力。在动物模型中，抗原物质被放置在前房（a.c.b）。眼睛引起系统性免疫反应，这是非常不寻常的，因为有选择性缺乏延迟型超敏反应（DTH， Th1反应的一个指标）。虽然这个模型已经得到了很好的研究，但还没有人研究过产生和维持眼部Th2反应的早期机制。我们提出，表达自然杀伤（NK）抗原的两种不同的淋巴细胞亚群可能参与对前房接种抗原的极性反应的早期调节。我们实验室最近的数据显示，ACID不会在CD1缺陷小鼠中发生。本应用程序将通过研究NKT细胞和CD1的机制和相互作用来利用这一观察结果。我们将使用多种方法来验证这些假设，包括流式细胞术，同时标记细胞内细胞因子和表面标记物，组织和悬浮液中细胞的形态学分析，分子生物学技术，包括rna保护试验。此外，我们将评估NK抗原阳性淋巴细胞在全动物模型中的作用，这些模型被操纵以预防ACID，并比较幼稚和引物小鼠的ACAID。这些研究成果将为理解眼部免疫偏差的细胞机制提供新的信息，并为NKT（先天免疫）和适应性免疫反应的相互作用提供新的见解。

Immunologists have known for decades that immunity is the result of the various contributions of cell-mediated and antibody-mediated responses. Within recent years the dichotomy of possible immune responses has been further defined by the knowledge that T helper cells can adopt one of two polar types of reactivity: T helper 1 (Th1) and T helper 2 (Th2). These counter responses can be differentiated by differences in the phenotype of cytokines (Th1, IFNgamma; Th2, IL4, IL10) and isotypes of antibodies (Th1: IgG2a; Th2: IgG1, IgE) they make. Th1 responses are associated with inflammation, while Th2 responses are associated with inflammation, while Th2 responses associated with hypersensitivity and protection against parasitic invasion. Because these two polar responses cross regulate each other it is possible that Th2 responses might be important in the prevention of inflammation in various organs including the eye. Apparently, in the health eye, it is very difficult to induce a Th1 response because of an unusual local regulatory mechanism in the anterior chamber. This research proposal will study the ocular regulatory mechanism known as Anterior Chamber Associated Immune Deviation (ACAID). ACAID is relevant to the up-regulation of Th2 responses and the down regulation of Th1 responses, i.e. inflammation, thereby preserving sight. In an animal model antigenic materials that are placed in the anterior chamber (a.c.) Of the eye evoke a systemic immune response that is distinctly unusual in there is a selective deficiency of delayed-type hypersensitivity (DTH, an indicator of a Th1, response). While this model is well studied, no one has looked at early mechanisms that might be invoked to produce and maintain an ocular Th2 response. We propose that two distinct subpopulations of lymphocytes expressing natural killer (NK) antigens may participate in the early regulation of the polar responses to antigens inoculated into the anterior chamber. Recent data from our laboratory show that ACID does not develop in CD1 deficient mice. This application will exploit this observation by studying the mechanisms and interaction of NKT cells and CD1. We will use a variety of methods to test the hypotheses including flow cytometry with simultaneous labeling of intracellular cytokines and surface markers, morphological analysis of cells in tissues and suspension, molecular biology techniques, including Rnase protection assay. In addition we will evaluate the role of NK antigen positive lymphocytes in whole animal models that are manipulated to prevent ACID and compare ACAID in naive and primed mice. Resents of the studies will generate new information toward understanding the cellular mechanisms of immune deviation in the eye and new insights into the interactions of NKT (innate immunity) and the adaptive immune response.