Regulation of ACAID by lymphocytes with NK markers

对自身抗原和外来抗原的耐受是一个主动过程， 机制等中心耐受性通过负选择或中心缺失一个大的 能够对自身分子起反应的淋巴细胞数量。然而，一些自我反应 淋巴细胞逃避这一过程，并保持存在于成人中，必须由活性调节。 涉及T调节细胞、无反应性或凋亡的耐受机制。在这里，我们将研究一个 外周耐受模型，可通过眼睛诱导，称为前房 相关免疫偏离（ACAID）。眼睛是一个免疫特权部位， 表现出免疫抑制机制，防止免疫炎症反应， 为了保护视力。为了更好地理解我们如何适应ACAID 眼自身免疫性疾病的免疫治疗机制，我们的第一个目标将调查 致敏小鼠与未致敏小鼠中ACAID诱导的机制。在这些研究中，我们将 还在接受角膜移植或其中 实验性自身免疫性葡萄膜炎是通过转移体外产生的ACAID样 免疫耐受原性APC，并探讨NKT细胞在这种治疗中的作用。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.