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FUNCTIONAL STUDIES OF HUMAN EPIDERMAL LANGERHANS CELLS

人表皮朗格汉斯细胞的功能研究

基本信息

批准号：
3153039
负责人：
MARILYN S POLLACK
金额：
$ 7.93万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-09-30 至 1986-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3153039
关键词：
Langerhans' cell T lymphocyte cell cell interaction flow cytometry histocompatibility antigens histocompatibility typing human subject immunogenetics leukocyte activation /transformation monoclonal antibody surface antigens tissue /cell culture

项目摘要

This proposed research project involves the intensive study of the functional properties of human Langerhans cells, with special reference to functional properties related to their expression of allospecific HLA-DR antigens. Human epidermal Langerhans cells have been known to express DR alloantigens and to possess Fc and C3b receptors character istic of cells of the monocyte/macrophage lineage. However, while some experimental evidence supports assignment of specific immunological functions such as stimulation of allogeneic lymphocyts and accessory cell functions, to guinea pig Langerhans cells, such functional activities have not yet been studied in relation to human Langerhans cells. Our laboratory has now developed a procedure for significant enrichment of Langerhans cells. This procedure, will be further improved and, together with our laboratory's extensive resources and experience in studies of human histocompatibility complex, will be used to accomplish the specific objectives of this proposal. In particular, the proposed research project will involve functional assays of the DR antigens on Langerhans cells as stimulators of primary and secondary allogeneic lymphocyte proliferation and as stimulators and targets of allospecific cytotoxic effector cells. The project will also involve studies of subpopulations of Langerhans cells with different surface markers, studies of other Langerhans cell surface antigens, identified by monoclonal antisera, and functional studies of the possible role of Langerhans cells as accessory cells for T-cell responses to mitogens and antigens. The properties studies will be attributed to Langerhans cells on the basis of comparative effects of enriched and depleted cells fractions and on the basis of effects of Langerhans cell elimination and surface marker blocking. In all these studies, the role of HLA-A,B,C and/or D/DR compatibility will be evaluated in relation to Langerhans cell interactions with other cell types and to the possible role of non-HLA antigens expressed on the Langerhans cells or other epidermal cell types. A better understanding of Langerhans cell functions will contribute to the general understanding of immunological diseases of the skin and of the role these cells may play in the initiation of graft versus host disease in patients receiving therapeutic allogeneic bone marrow transplantation.

本拟议的研究项目涉及对人类朗格汉斯细胞的功能特性，特别是与其同种异体特异性 HLA-DR 表达相关的功能特性抗原。已知人类表皮朗格汉斯细胞表达 DR 同种异体抗原并具有细胞的Fc和C3b受体特征单核细胞/巨噬细胞谱系。然而，虽然一些实验有证据支持特定免疫功能的分配，例如刺激同种异体淋巴细胞和辅助细胞功能，豚鼠朗格汉斯细胞，这种功能活动尚未被证实研究了与人类朗格汉斯细胞的关系。我们实验室现在有开发了一种显着富集朗格汉斯细胞的程序。这程序将进一步改进，并与我们实验室的在人类组织相容性研究方面拥有丰富的资源和经验复杂，将用于实现此特定目标提议。特别是，拟议的研究项目将涉及朗格汉斯细胞上 DR 抗原作为刺激物的功能测定原发性和继发性同种异体淋巴细胞增殖和同种异体特异性细胞毒性效应细胞的刺激物和靶标。这该项目还将涉及朗格汉斯细胞亚群的研究使用不同的表面标记，对其他朗格汉斯细胞表面的研究通过单克隆抗血清鉴定的抗原及其功能研究朗格汉斯细胞作为 T 细胞反应辅助细胞的可能作用促有丝分裂原和抗原。属性研究将归因于朗格汉斯细胞基于富集和富集的比较效果耗尽的细胞分数并基于朗格汉斯细胞的影响消除和表面标记阻断。在所有这些研究中， HLA-A、B、C 和/或 D/DR 兼容性将根据以下方面进行评估朗格汉斯细胞与其他细胞类型的相互作用以及可能的作用朗格汉斯细胞或其他表皮上表达的非 HLA 抗原细胞类型。更好地了解朗格汉斯细胞功能将有助于对免疫性疾病的普遍了解皮肤以及这些细胞在移植物抗反应启动中可能发挥的作用接受治疗性同种异体骨髓的患者的宿主疾病移植。