IMMUNOREGULATORY T CELLS IN TRANSPLATATION TOLERANCE

诱导供体对宿主组织耐受的克隆抑制性T淋巴细胞 在移植免疫学的研究中将是有用的， 免疫调节 该项目整合了体内和体外技术 对克隆的免疫调节抑制因子T 细胞移植耐受性。 将使用抑制子样T细胞 定义抑制表现的免疫遗传学要求 在体内和体外，并获得免疫学的理解， 参与抑制的代谢机制。 原型克隆（SAC-A9） 已经从无菌异基因骨髓嵌合体中分离出来 （ABMC）具有抑制的抗宿主反应性。 这些克隆人将 以表达细胞表面抗原、淋巴因子 受体和淋巴因子的产生。 我们假设SAC-A9或 类似的细胞可能参与维持体内供体-宿主耐受性。 克隆在体内的迁移模式和功能寿命 存在和不存在特异性抗原刺激和/或外源性IL-2 将被审查。 有限稀释增殖和细胞毒性测定， MLC/CML测定、体外淋巴因子抑制测定和白血病 体内排斥反应将用于评价同种异体反应性的抑制， 正常小鼠和给予克隆的抑制细胞的ABMC。 克隆能力 在体内预防或治疗移植物抗宿主病抑制细胞将 被研究。

Cloned suppressor T lymphocytes that induce donor tolerance to host tissues in vivo would be useful in studies on transplantation immunology and immunoregulation. This project integrates in vivo and in vitro techniques into a systematic study of the role of cloned immunoregulatory suppressor T cells in transplantation tolerance. Suppressor-like T cells will be used to define the immunogenetic requirements for manifestation of suppression in vivo and in vitro and to gain an understanding of the immunologic and metabolic mechanisms involved in suppression. Prototype clones (SAC-A9) have been isolated from bacteria-free allogeneic bone marrow chimeras (ABMC) with suppressed antihost reactivity. These clones will be characterized as to expression of cell surface antigens, lymphokine receptors and production of lymphokines. We hypothesize that SAC-A9 or similar cells may be involved in maintaining donor-host tolerance in vivo. The migration pattern and functional life-span of clones in vivo in the presence and absence of specific antigen stimulation and/or exogenous IL-2 will be examined. Limiting dilution proliferation and cytotoxicity assays, MLC/CML assays, lymphokine-inhibition assays in vitro and leukemia rejection in vivo will be used to evaluate suppression of alloreactivity in normal mice and ABMC given cloned suppressor cells. The ability of cloned suppressor cells to prevent or treat graft-versus-host disease in vivo will be studied.