MECHANISMS OF TOLERANCE AND AUTOIMMUNITY IN THE EYE

描述（改编自申请人的摘要）：考虑眼睛 是一个免疫特权区， 必须抑制威胁性免疫反应。 本申请提出 研究通过研究基本机制来调查这个问题， T细胞识别并响应存在于眼睛中的抗原。 在 第一个目标，采用卵清蛋白（OVA）的新型过继转移系统， 来自DO11.10 TCR转基因小鼠的特异性T细胞将用于研究 淋巴和脾引流的眼睛，并确定的作用， 眼内抗原呈递细胞（APC）在呈递来自 眼睛 在第二个目标中，将产生表达OVA的转基因小鼠。 作为自身抗原的模型。 OVA特异性T细胞的能力 以各种方式激活，以响应外源性或 将研究内源性OVA。 Fas配体表达在细胞凋亡中的作用 对浸润细胞凋亡诱导的关注将是 测定 在第三个目标中，转基因小鼠表达分泌的或 视网膜中的膜OVA将与DO11.10 TCR转基因杂交 小鼠或通过过继转移给予的DO11.10 T细胞， 将评估耐受性诱导的细胞机制。

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.