ANTERIOR CHAMBER INFLUENCE ON OCULAR ANTIGENS

描述（改编自申请人摘要）：全身免疫反应 前房抗原是异常的，因为某些类型的免疫效应物 （迟发型超敏反应和补体结合抗体）选择性地 抑制，而其他效应细胞（细胞毒性T细胞，非补体固定 抗体）被保留。这种反应模式被称为前 室相关免疫偏离（ACAID）。这种现象的机制 涉及通过眼抗原形成对眼抗原的初始应答， 微环境，因此，调节细胞出现，决定类型的 响应生成。如果眼睛因炎症、创伤或疾病而改变， 其促进反歧视和不容忍协会的能力被取消。提出的实验方案 解决了3个相关的假设，同时利用卵清蛋白T细胞受体 (OVA TCR）转基因小鼠：（i）OVA特异性TCR转基因T细胞， 在体外由OVA脉冲的TGF-β 2处理的抗原呈递细胞活化 (APC)，成为调节性T细胞，分别抑制诱导和 迟发性超敏反应在体内的表达;（ii）色素上皮 抑制Th 1型细胞的活化，并将活化的T细胞转化为 调节细胞;和（iii）免疫赦免和ACAID被废除 急性眼部炎症，但次要机制干预，以恢复 免疫抑制和ACAID。这些假设产生了3个具体目标： (1)表征和描述ACAID的调节性T细胞的作用模式; (2)描述促进免疫赦免的眼部因素的作用模式 和正常眼的ACAID;和（3）确定炎症的后果 和外伤对眼部免疫豁免的影响 研究人员认为，实验计划将提供关键的 关于眼部免疫豁免和ACAID的分子基础的信息 在正常小鼠中，并将揭示消除免疫的分子过程 并允许它恢复。第二个好处是 显著扩展了对差异调节基因的了解 在诱导和表达ACAID的细胞过程中。的 预期是关于ACAID和免疫关键基因的新知识， 特权将导致针对减轻眼的治疗策略 炎性疾病和促进原位移植物接受。

DESCRIPTION (Adapted from applicant's abstract): Systemic immune responses to anterior chamber antigens are deviant in that certain types of immune effectors (delayed hypersensitivity and complement-fixing antibodies) are selectively suppressed, whereas other effectors (cytotoxic T cells, non-complement fixing antibodies) are retained. This pattern of response has been termed Anterior Chamber Associated Immune Deviation (ACAID). The mechanisms of this phenomenon involve shaping of the initial response to ocular antigens by the ocular microenvironment, so that regulatory cells arise that dictate the type of response generated. If the eye is altered by inflammation, trauma or disease, its capacity to promote ACAID is abolished. The experimental plan proposed addresses 3 related hypotheses, while making use of ovalbumin T cell receptor (OVA TCR) transgenic mice: (i) that OVA-specific TCR transgenic T cells, activated in vitro by OVA-pulsed TGF-beta2-treated antigen presenting cells (APC), become regulatory T cells that suppress, respectively, the induction and expression of delayed hypersensitivity in vivo; (ii) that pigment epithelium inhibits activation of Th1-type cells and converts activated T cells into regulatory cells; and (iii) that immune privilege and ACAID are abolished acutely in ocular inflammation, but secondary mechanisms intervene to restore immune suppression and ACAID. These hypotheses give rise to 3 specific aims: (1) to characterize and describe mode of action of regulatory T cells of ACAID; (2) to describe mode of action of ocular factors that promote immune privilege and ACAID in normal eyes; and (3) to determine the consequences of inflammation and trauma on ocular immune privilege. The investigators contend that the experimental plan will provide key information concerning the molecular basis of ocular immune privilege and ACAID in the normal mouse, and will reveal molecular processes that abolish immune privilege and allow it to be restored. A secondary benefit will be a significant expansion of knowledge of genes that are differentially regulated in the cellular processes by which ACAID is induced and expressed. The anticipation is that new knowledge concerning key genes in ACAID and immune privilege will lead to therapeutic strategies directed at alleviating ocular inflammatory disease and promoting orthotopic graft acceptance.