SIGNIFICANCE OF IMMUNOLOGICAL SEQUESTRATION IN THE EYE

描述：(摘自摘要)。 眼睛含有免疫特权组织。免疫特权指的是 免疫反应的衰减性在某些组织中提供资金，例如眼睛。 免疫特免权被认为使眼睛能够对抗原做出反应 在保护视力所依赖的微妙结构方面的挑战。 眼睛的免疫特免权很久以前就被观察到了，但目前还不清楚。一个 关于眼睛免疫豁免机制的长期问题是 定位导致的被动免疫耐受--隔离的作用 解剖屏障后面的抗原。在眼里，这些障碍包括 视网膜血管内皮细胞和视网膜色素上皮，它们构成了 “血/视网膜屏障。”隔离被认为是为了减少淋巴 仔细观察视网膜，最大限度地减少抗原从该组织中的泄漏。缺席 免疫系统和抗原之间的相互作用可能导致对 那些抗原。目前对眼睛免疫赦免的研究大多集中在 阐明耐受的活动机制，称为免疫偏离，称为 自动减支的意义受到质疑。 视网膜脱离在视网膜免疫豁免中的作用 正常的动物一直很难，因为没有足够的阴性对照 可用的，分析需要比较以下动物的免疫反应 在隔离部位与非隔离部位表达抗原，尤其是在 缺乏对血-视网膜屏障的机械妥协。vbl.使用 遗传方法，我们实现这些的两个实验策略 条件是富有成效的。PI报告转基因(TG)表达 小鼠视网膜中的β-半乳糖苷酶(b-GAL)为 B-半乳糖介导C04 T细胞的EAU，但小鼠对B-半乳糖不耐受， 除非抗原特异的、激活的C04 T细胞是 养大的。他的另一种方法显示了UM逆转录病毒转导大鼠视网膜 S-Ag(A/K/A arrestin)基因导入大鼠骨髓来源细胞导致缺失 大鼠S-银多肽诱导EAU的敏感性。直截了当的 结论是隔离抑制了主动耐受的诱导 视网膜抗原，并在很大程度上有助于视网膜免疫豁免 正常的眼睛。 重要的问题仍然存在，他建议继续使用TG小鼠。 首先，我们观察到的缺乏宽容的现象可以用以下几点来解释： 佐剂驱动的免疫，或活化的CD4T的过继转移 细胞，压倒了现有的、活跃的耐受机制。使用T细胞 受体TG小鼠，我们将询问是否原始的针对b-Gal的CD4T细胞 在正常或受损或发炎的眼睛中暴露于视网膜b-GAL。如果是，是什么？ 结果是什么？PI将把这些问题扩展到CD8 T细胞。第二，因为 有效的主动眼睛免疫偏离机制已经在实验中被 诱导，它们适用于正常眼睛吗？第三，我们对自动减支的研究 到目前为止，这一点很重要，主动机制是否为 受损或发炎的眼睛会出现隔离吗？

DESCRIPTION: (from abstract). The eye contains immune privileged tissues. Immune privilege refers to the attenuated nature of immune responses fund in certain tissues, such as the eye. Immune privilege is thought to enable the eye to respond to antigenic challenges in ways that preserve delicate structures upon which vision depends. Immune privilege of the eye was observed long ago, but is not yet understood. A long standing question concerning mechanisms of ocular immune privilege is the role of sequestration, the passive immune tolerance attributed to localization of antigens behind anatomic barriers. In the eye, these barriers include the retinal vascular endothelium and retinal pigment epithelium, which comprise the "blood/retinal barrier." Sequestration was postulated to reduce lymphatic perusal of retina and minimize leakage of antigens from this tissue. Absence of interaction between the immune system and antigens can lead to ignorance of those antigens. Most current studies of ocular immune privilege concentrate on elucidating active mechanisms of tolerance, termed immune deviation, calling the significance of sequestration into question. Assessment of the contribution of sequestration to retinal immune privilege in normal animals has been difficult because adequate negative controls were not available, analysis requires comparison of immune responses of animals that express an antigen in sequestered versus non-sequestered sites, especially in the absence of mechanical compromises to the blood-retinal barrier. Using genetic approaches, our two experimental strategies for achieving these conditions have been fruitful. The PI reported that transgenic (Tg) expression of beta-galactosidase (b-gal) in mouse retina created a target for b-gal-mediated EAU by C04 T cells, but the mice were not tolerant to b-gal, appealing ignorant of it unless antigen-specific, activated C04 T cells were raised. His other approach showed UM retroviral transduction of the rat retinal S-Ag (A/K/A arrestin) gene into rat bone marrow-derived cells led to loss of susceptibility to EAU induction by rat S-Ag peptides. The straight-forward conclusion is that sequestration inhibits induction of active tolerance by retinal antigens, and contributes substantially to retinal immune privilege in normal eyes. Important questions remain, and he proposes to continue using the Tg mice. First, our observation of a lack of tolerance could be explained by proposing that adjuvant-driven immunization, or adoptive transfer of activated CD4 T cells, overwhelmed existing, active mechanisms of tolerance. Using T cell receptor Tg mice, we will ask if naive CD4 T cells specific for b-gal become exposed to retinal b-gal in normal or damaged, or inflamed eyes. If so, what is the outcome? The PI will extend these questions to CD8 T cells. Second, since potent active ocular immune deviation mechanisms have been experimentally induced, do they apply to normal eyes? Third since our studies of sequestration to date show it to be important, do active mechanisms provide "back-up' for sequestration in damaged or inflamed eyes?