CORNEAL ENDOTHELIAL CELL IMMUNOREGULATORY FACTORS

描述（改编自申请人摘要）：免疫应答很重要 保护免受入侵的病原体，但这些反应有可能 对周围正常组织造成非特异性损伤。虽然许多组织 很好地耐受非特异性损害，不会遭受永久性后果， 其他部位，如眼睛和大脑，具有精细的显微解剖结构， 完整性和功能很容易被破坏。据了解，这些网站有 开发了改变免疫反应以最小化炎症的能力， 其后果;即他们是免疫特权。 很久以前，免疫赦免被描述为同种异体免疫系统的观察结果。 组织移植物在置于免疫豁免部位时存活得非常好， 例如眼前房、大脑、睾丸和胎盘。为 几十年来，免疫学家们对这种特权仅仅是 由于免疫无知，由于这些之间的物理障碍， 抗原和免疫系统。然而，在过去的15年里，一些活跃的 已经描述了机制，表明对抗原的无知是 对维持免疫特权的关注使得 很明显，它的生物学意义是很高的，即使机制 仍在进一步研究中 全身和局部效应都与维持免疫有关。 眼睛的特权以前，我们报道了角膜内皮细胞（CE） 细胞抑制抗原和丝裂原活化的淋巴细胞增殖测定， 尽管IL-2 R表达和对外源IL-2的反应性不受影响。 为了进一步检查这种活性，将CE细胞和T细胞克隆共培养， 研究了CE细胞选择性地抑制T细胞产生1 L-2和1 L-4 细胞，但不是11-5或11-6生产。T细胞与CE细胞的预孵育， 或CE细胞条件培养上清液，抑制细胞内钙离子浓度 T细胞抗原受体连接诱导的增加，导致 抑制NFAT依赖性细胞因子产生。我们还发现了另外两个 CE细胞对T细胞的影响;培养物中的淋巴细胞活力通过 CE细胞因子和一些T细胞表面标志物的表达，如 与CE细胞孵育后，CD 8 α、Thy 1和CD 45 RC发生改变，或 条件培养基 介导这些的因素的识别和表征 新的影响是本研究的目标。我们建议：1.使用表达式 克隆CE细胞文库以发现活性; 2.识别 活动，以了解它是否是已知因素;以及3.如果活动没有 如前所述，继续对因子进行表征， 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.