STUDIES ON THE IMMUNOLOGICAL BASIS OF FETAL TOLERANCE

胎儿耐受性的免疫学基础研究

• 批准号: 3328694
• 负责人: ARTHUR MALLEY
• 金额: $ 13.84万
• 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/3328694
• 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.

我们的假设是，蜕膜细胞分泌的CSF-1 在胎儿发育过程中提供了一个“环境”， 诱导抗原特异性T抑制（Ts）细胞。 早期研究 在我的实验室里，证明了外源抗原在 妊娠不仅在后代中诱导抗原特异性Ts细胞， 而且这些Ts细胞在分娩后持续存在16周。 我们 研究还证实了蜕膜巨噬细胞在 成功怀孕 拟议的研究将试图 描述蜕膜巨噬细胞和Ts细胞的发育 在胎儿期针对亲本和外源抗原 发展 怀孕最后三个月的产妇免疫 代表了一个重要的！为母亲和母亲提供保护的手段 和婴儿对病原性病毒和细菌。 的可能性 γ干扰素（γ-IFN）治疗沿着免疫接种， 怀孕的最后三个月，以加强双方的免疫反应， 母亲和胎儿为新生儿提供更好的保护， 关于亲本抗原和外来抗原进行了探索。 抗原特异性Ts细胞的长持续时间为16周后， 关于记忆Ts细胞的可能性的问题。 实验 旨在确定AgB特异性Ts细胞的持久性是否诱导了 在胎儿发育期间，可以延长到分娩后16周以上， 在丧失耐受性之前的不同时间进行免疫接种，以及 将努力确定记忆Ts细胞是否是T抑制细胞之一或两者都是 诱导物效应物 尝试分离和表征受体上 抗原特异性Ts细胞一直不成功。 最近的几项研究 提示Ts细胞先于T细胞发育 与辅助性T细胞或细胞毒性T细胞相关的TcR， Ts细胞上的TcR是不同的 我们建议扩大AgB特异性Ts 通过在抗Tsfi抗体包被的培养皿上淘选来自新生儿的细胞， 并将这些细胞与BW 5147 T细胞融合。 AgB特异性Tsi细胞 通过有限稀释法克隆的细胞将通过在 中空纤维培养室，以提供两个显著增加 它们的绝对细胞数和这些细胞分泌的可溶性因子 可以用于其表征的细胞。