HUMAN CYTOTOXIC LYMPHOCYTES IN IMMUNE DISORDERS

组织和循环中淋巴细胞亚群与临床免疫 疾病已经根据膜抗原表型来表征。 这些发现表明，存在异常数量的辅助/诱导物或 细胞毒性/抑制细胞。 然而，由于目前的单克隆抗体 与细胞毒性和抑制细胞反应，它经常是模糊的 因为细胞相对缺乏或过剩。 我们最近 开发了一种抗人T细胞的鼠单克隆抗体（抗Cyt-1 参与细胞毒性T细胞（CTL）应答但不参与 镇压 它与富含CTL的悬浮液反应， 急性移植物抗宿主病靶组织浸润淋巴细胞 疾病（GVHD），并且耗尽Cyt-1+细胞的应答细胞不能 在混合淋巴细胞培养物中产生CTL，但不产生特异性 抑制细胞 我们在此建议充分表征淋巴细胞 由该抗体、膜表型、抗原定义的亚群 特异性和杀伤机制，以分离和鉴定 相关抗原和与成熟和功能相关的抗原密度， 研究组织中淋巴细胞浸润的免疫病理学， 最后，为了更好地定义T淋巴细胞亚群， 抗体的 本提案中使用的技术包括克隆 杂交瘤，混合淋巴细胞培养物，间接免疫过氧化物酶，和 荧光激活细胞分选。 这两个长期目标 研究是为了更好地确定诊断样本中的免疫失衡， 并了解CTL反应及其调节。

Subpopulations of lymphocytes in tissue and circulation in clinical immune disorders have been characterized according to membrane antigen phenotype. These findings suggest that there are abnormal numbers of helper/inducer or cytotoxic/suppressor cells. However, because present monoclonal antibodies react with both cytotoxic and suppressor cells, it is frequently ambiguous as which cells are relatively deficient or in excess. We have recently developed a mouse monoclonal antibody (anti-Cyt-1) against human T lymphocytes participating in the cytotoxic T cell (CTL) response but not in suppression. It reacts with suspensions enriched with CTL, stains the infiltrating lymphocytes of target tissues with acute graft-versus-host disease (GVHD), and responder cells depleted of Cyt-1+ cells fail to develop CTL in a mixed lymphocyte culture but do develop specific suppressor cells. We propose herein to fully characterize the lymphocyte subpopulation defined by this antibody, membrane phenotype, antigen specificity and mechanism of killing, to isolate and chracterize the associated antigen and relate antigen density to maturation and function, to study the immunopathology of lymphocyte infiltrates in tissues, and finally to better define the subpopulations of T lymphocytes using this antibody. The techniques used in this proposal include cloning of hybridomas, mixed lymphocyte cultures, indirect immunoperoxidase, and fluorescence activated cell sorting. Two long term objectives of these studies are to better define the immune imbalance in diagnostic specimens, and understand the CTL response and its regulation.