STUDIES ON THE IMMUNOLOGICAL BASIS OF FETAL TOLERANCE

胎儿耐受性的免疫学基础研究

• 批准号: 3328696
• 负责人: ARTHUR MALLEY
• 金额: $ 13.97万
• 依托单位: OREGON REGIONAL PRIMATE RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3328696
• 关键词: T cell receptor; colony stimulating factor; cytotoxic T lymphocyte; embryo /fetus membrane; flow cytometry; growth /development; hollow fiber separation technique; hybridomas; hypersensitivity; immune tolerance /unresponsiveness; immunologic memory; immunosuppression; interferons; interleukin 2; laboratory mouse; leukocyte activation /transformation; macrophage; natural killer cells; perinatal; pregnancy immunology; suppressor T lymphocyte; tissue /cell culture

Our hypothesis suggests that CSF-1 secreted by decidual cells provides an "environment" during fetal development resulting in the induction of antigen-specific T suppressor (Ts) cells. Earlier studies in my laboratory demonstrated that foreign antigen administered during pregnancy not only induced antigen-specific Ts cells in the offspring, but also these Ts cells persisted for 16 weeks after delivery. Our studies also demonstrated the importance of decidual macrophages in successful pregnancies. The proposed studies will attempt to characterize decidual macrophages, and the development of Ts cells directed against both parental and foreign antigens during fetal development. Maternal immunization during the last trimester of pregnancy represents an important !means of providing protection to both the mother and infant against pathogenic virus and bacteria. The possibility of gamma interferon (gamma-IFN) treatment along with immunization during the last trimester of pregnancy to enhance the immune response of both, the mother and fetus providing enhanced protection for the neonate will be explored with regards to both parental and foreign antigens. The long persistence of antigen-specific Ts cells for 16 wks after questions regarding.the possibility of memory Ts cells. Experiments are designed to determine if the persistence of AgB-specific Ts cells induced during fetal development can be extended beyond 16 wks after delivery by immunization of various times prior to the loss of their tolerance, and efforts will determine if memory Ts cells are either or both T suppressor inducer effector. Attempts to isolate and characterize the receptors on antigen-specific Ts cells have been unsuccessful. Several recent studies suggest that Ts cells develop prior to the development of T cell receptors (TcR) associated with T helper or cytotoxic T cells suggesting that TcR on Ts cells are distinct. We propose to expand AgB-specific Ts cells from neonates by panning on anti-Tsfi antibody coated petri dishes, and fusing these cells with BW5147 T cells. AgB-specific Tsi cells cloned by limiting dilution will be further expanded by culturing in hollow fiber culture chambers to provide a significant increase in both their absolute cell numbers and the soluble factors secreted by these cell which can be used for their characterization.

我们的假设表明，蜕膜细胞分泌的CSF-1 在胎儿发育过程中提供一个“环境”，导致 抗原特异性T抑制(TS)细胞的诱导。早期研究 在我的实验室里证明了外源抗原是在 怀孕不仅会在后代体内诱导出抗原特异性的ts细胞， 而且这些TS细胞在分娩后持续了16周。我们的 研究还表明蜕膜巨噬细胞在子宫内膜中的重要性。 成功怀孕。拟议的研究将试图 蜕膜巨噬细胞的特性和TS细胞的发育 在胎儿时期针对双亲和外源抗原 发展。 孕期最后三个月的孕产妇免疫接种 代表着一种重要的！保护母亲和母亲的手段 和婴幼儿对抗致病病毒和细菌。是否有可能 干扰素(γ-干扰素)治疗与免疫同时进行 怀孕的最后三个月来增强双方的免疫反应， 母亲和胎儿将加强对新生儿的保护 关于亲本抗原和外源抗原的探索。 16周后抗原特异性ts细胞的长期存留 关于记忆TS细胞的可能性。实验是 旨在确定Agb特异性ts细胞的持久性是否能诱导 在胎儿发育期间可以延长到分娩后16周以上 免疫前不同时间对其失去耐受性，以及 努力将确定记忆ts细胞是T抑制者之一还是两者都是 诱导器效应器试图分离和鉴定细胞上的受体 抗原特异的ts细胞一直没有成功。最近的几项研究 提示TS细胞在T细胞发育之前发育 与辅助性或细胞毒性T细胞相关的受体(TCR)提示 TS细胞上的TCR是不同的。我们建议扩展特定于AGB的TS 通过在涂有抗TSFI抗体的培养皿上淘洗来自新生儿的细胞， 并将这些细胞与BW5147 T细胞融合。AGB特异性TSI细胞 通过限制稀释法克隆的克隆将通过在 中空纤维培养箱显著增加了这两个 它们的绝对细胞数和由它们分泌的可溶性因子 可用于表征它们的单元格。