ANTERIOR CHAMBER INFLUENCE ON OCULAR ANTIGENS

描述(改编自申请人的摘要)：系统免疫反应 前房抗原在某些类型的免疫效应器中是不同的 (迟发型超敏反应和补体固定抗体)是选择性的 抑制，而其他效应器(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反应。 小室相关免疫偏离(ACAID)。这一现象产生的机制 包括眼部对眼部抗原的初始反应的形成 微环境，所以调控细胞的出现决定了 已生成响应。如果眼睛因炎症、创伤或疾病而改变， 其促进ACAID的能力被废除。提出了实验计划 在利用卵蛋白T细胞受体的同时，解决了3个相关的假设 (OVA TCR)转基因小鼠：(1)OVA特异性TCR转基因T细胞， 卵清蛋白冲击的转化生长因子-β2处理的抗原提呈细胞体外激活 (APC)，成为调节性T细胞，分别抑制诱导和 迟发型超敏反应在体内的表达；(Ii)色素上皮 抑制Th1型细胞的激活，并将激活的T细胞转化为 调节细胞；和(Iii)取消免疫豁免和ACAID 严重的眼部炎症，但二级机制干预恢复 免疫抑制和ACAID。这些假设产生了3个具体目标： (1)鉴定和描述ACAID调节性T细胞的作用模式； (2)描述促进免疫赦免的眼睛因素的作用方式 和正常眼的ACAID；(3)确定炎症的后果 和眼睛免疫特许权上的创伤。 调查人员争辩说，实验计划将提供关键 眼免疫赦免和ACAID的分子基础研究进展 在正常小鼠中，并将揭示取消免疫的分子过程 特权并允许其恢复。第二个好处将是 差异调控基因知识的显著扩展 在诱导和表达ACAID的细胞过程中。这个 预期是关于ACAID和免疫关键基因的新知识 特权将导致针对缓解眼部症状的治疗策略 炎症性疾病和促进原位移植物接受性。

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.