CORNEAL ENDOTHELIAL CELL IMMUNOREGULATORY FACTORS

描述(摘自申请者的摘要)：免疫反应很重要 以防止入侵病原体，但这些反应具有潜在的 在周围正常组织中产生非特异性损伤。虽然很多纸巾 能容忍非特定的损害，不会遭受永久性的后果， 其他部位，如眼睛和大脑，拥有精细的显微解剖结构，其 完整性和功能很容易损坏。据了解，这些网站有 开发了改变免疫反应以最大限度地减少炎症和 其后果；即他们享有豁免权。 免疫豁免很久以前就被描述为观察到同种异体 当组织移植物被放置在免疫特权部位时，存活得异常好， 如眼前房、脑、睾丸和胎盘。为 几十年来，免疫学家们对这一特权仅仅是 是由于免疫无知造成的，因为它们之间的物理屏障 抗原和免疫系统。然而，在过去的15年里，有几个活跃的 机制已被描述，表明对抗原的无知是 对维护免疫豁免权的重视不够使 很明显，它的生物学意义很高，尽管它的机制 目前仍在澄清中。 全身和局部的影响都与维持免疫有关。 眼睛的特权。先前，我们报道了角膜内皮细胞(CE) 细胞抑制抗原和有丝分裂原激活的淋巴细胞增殖试验， 虽然IL-2R的表达和对外源1L-2的反应性没有受到影响。 为了进一步研究这种活性，将CE细胞和T细胞克隆进行共培养 ，并对其进行了研究。CE细胞选择性抑制T细胞产生1L-2和1L-4 细胞，但不是11-5或11-6的产物。T细胞与CE细胞的预培养， 或CE细胞条件培养上清，抑制细胞内钙离子 通过结扎T细胞抗原受体诱导的增加，导致 抑制NFAT依赖的细胞因子的产生。我们还发现了另外两个 CE细胞对T细胞的影响；培养的淋巴细胞活性被提高 一种CE细胞因子，以及一些T细胞表面标志的表达，如 CD8α、Thy 1和CD45RC在与CE细胞孵育或 条件培养液。 中介因子(S)的鉴定与表征 新颖的效果是本研究的目标。我们建议：1.使用表达式 克隆CE细胞库以寻找活性(S)；2.鉴定 活动(S)了解它是否是已知因素(S)；以及3.如果活动没有 已描述，继续表征因素(S)和 作用机制。

DESCRIPTION (Adapted from applicant's abstract): Immune responses are important for protection from invading pathogens, but these responses have the potential to produce nonspecific injury in surrounding normal tissues. While many tissues tolerate nonspecific damage well and do not suffer permanent consequences, other sites such as the eye and brain, possess a delicate microanatomy whose integrity and function are easily damaged. It is known that these sites have developed the ability to modify immune responses to minimize inflammation and its consequences; i.e. they are immune privileged. Immune privilege was described long ago as the observation that allogeneic tissue grafts survive unusually well when placed in immune privileged sites, such as the anterior chamber of the eye, the brain, testis and placenta. For decades, immunologists were satisfied with the idea that the privilege solely resulted from immune ignorance due to the physical barriers between these antigens and the immune system. However, in the last 15 years, several active mechanisms have been described, indicating that ignorance of the antigens is not sufficienl The attention paid to the maintenance of immune privilege makes it clear that its biological significance is high, even though the mechanisms are still being elucidated. Both systemic and local effects have been implicated in maintaining the immune privilege of the eye. Previously, we reported that corneal endothelial (CE) cells inhibited antigen- and mitogen-activated lymphocyte proliferation assays, although lL-2R expression and responsiveness to exogenous 1L-2 were unaffected. To further examine this activity, co-cultures of CE cells and T cell clones were studied. CE cells selectively inhibited 1L-2 and 1L-4 production by T cells, but not 11-5 or 11-6 production. Preincubation of T cells with CE cells, or CE cell-conditioned culture supernatant, inhibited the intracellular calcium increase induced by ligation of the T cell antigen receptor, leading to inhibition of NFAT-dependent cytokine production. We have also found two other effects of CE cells on T cells; lymphocyte viability in cultures is enhanced by a CE cell factor, and expression of some T cell surface markers, such as CD8alpha, Thy 1, and CD45RC are altered following incubation with CE cells or conditioned medium. The identification and characterization of the factor(s) that mediates these novel effects are the goals of this study. We propose to: 1. use expression cloning of a CE cell library to find the activity(s); 2. identify the activity(s) to learn if it is a known factor(s); and 3. if the activity has not already been described, continue characterization of the factor(s) and mechanism of action.