MECHANISMS OF TOLERANCE AND AUTOIMMUNITY IN THE EYE

描述(改编自申请者的摘要)：眼睛被视为 是一个免疫特权的地方，在那里可能会看到 必须抑制具有威胁性的免疫反应。此应用程序建议 研究通过研究基本机制来研究这一问题 T细胞识别眼睛中存在的抗原并对其做出反应。在……里面 第一个目标是一种使用卵清蛋白(OVA)的新型过继转移系统 来自DO11.10 TCR转基因小鼠的特定T细胞将用于研究 淋巴和脾从眼部引流并确定其作用 眼内抗原提呈细胞(APC)提呈人眼部抗原 眼睛。在第二个目标中，将生产出表达卵白蛋白的转基因小鼠。 在视网膜中作为模型自身抗原。卵清蛋白特异性T细胞的能力 以各种方式被激活以渗入眼睛以响应外源性或 将对内源性OVA进行研究。Fas配体表达在血管内皮细胞癌中的作用 在诱导浸润性细胞的凋亡方面，眼睛将是 下定决心。在第三个目标中，表达的转基因小鼠分泌或 视网膜中的膜OVA将与DO11.10 TCR转基因杂交 小鼠或给予DO11.10 T细胞的过继转移和程度 耐受性诱导的细胞机制将被评估。

DESCRIPTION (Adapted from the Applicant's abstract): The eye is considered to be an immunologically privileged site in which potentially sight threatening immune responses must be inhibited. This application proposes studies to investigate this issue by studying the basic mechanisms by which T-cells recognize and respond to antigens that are present in the eye. In the first aim, a novel adoptive transfer system employing ovalbumin (OVA) specific T-cells from the DO11.10 TCR transgenic mouse will be used to study lymphatic and splenic drainage from the eye and to determine the role of intraocular antigen presenting cells (APC) in presenting antigens from the eye. In the second aim, transgenic mice will be produced that express OVA in the retina as a model self antigen. The ability of OVA specific T-cells activated in various ways to infiltrate the eye in response to exogenous or endogenous OVA will be studied. The role of Fas ligand expression within the eye on the induction of apoptosis of the infiltrating cells will be determined. In the third aim, transgenic mice expressing either secreted or membrane OVA in the retina will be crossed with the DO11.10 TCR transgenic mouse or given DO11.10 T-cells by adoptive transfer and the degree and cellular mechanisms of tolerance induction will be assessed.