Regulation of ACAID by lymphocytes with NK markers

对自身和外源抗原的耐受是一个由多种因素介导的活跃过程。 机械装置。中心耐受性是通过大片段的负选择或中心缺失来促进的 能够对自身分子发生反应的淋巴细胞数量。然而，有些自我反应 淋巴细胞逃脱这一过程并保留在成人体内，必须由活性调节 耐受机制涉及T调节细胞、无能或细胞凋亡。在这里，我们将研究一个 可通过称为前房的眼部诱导的外周耐受模型 相关免疫偏离(ACAID)。眼睛是一种免疫特权部位，已经进化到 展示免疫抑制机制，以防止免疫炎症反应 眼睛是为了保护视力。为了更好地了解我们可能如何适应ACAID 眼部自身免疫性疾病的免疫治疗机制，我们的首要目标是研究 致敏小鼠与幼稚小鼠ACAID的诱导机制。在这些研究期间，我们将 也可以在接受角膜移植的小鼠或在 体外产生的ACAID样蛋白转移诱导实验性自身免疫性葡萄膜炎 耐受性APC，并探索NKT细胞在该治疗中的作用。这些研究的结果 将提高基于细胞的疗法治疗免疫性炎症性疾病的可能性 眼睛。

Tolerance to self and foreign antigens is an active process that is mediated by multiple mechanisms. Central tolerance is promoted by negative selection or central deletion of a large number of lymphocytes capable of reacting to self molecules. However, some self-reactive lymphocytes escape this process and remain present in the adult and must be regulated by active tolerance mechanisms that involve T regulatory cells, anergy, or apoptosis. Here, we will study a model for peripheral tolerance that can be induced through the eye called Anterior Chamber Associated Immune Deviation (ACAID). The eye is an immune privileged site that has evolved to exhibit immunosuppressive mechanisms that prevent immune inflammatory reactions in the eye in order to preserve vision. In order to better understand how we might adapt ACAID mechanism to immunotherapy of autoimmune disease in the eye, our first aim will investigate the mechanisms of ACAID induction in sensitized vs naïve mice. During these studies we will also induce antigen specific ACAID in mice that receive cornea transplants or in which experimental autoimmune uveitis is induced by transferring in vitro generated ACAID- like tolerogenic APC, and explore the role of the NKT cell in this therapy. The results of these studies will raise the possibility of a cell based therapy to treat immune inflammatory diseases in the eye.