IMMUNOLOGICAL CONSEQUENCES OF TRANSFUSION

输血的免疫学后果

• 批准号: 6389775
• 负责人: LOREN D. FAST
• 金额: $ 19.86万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6389775
• 关键词: B lymphocyte; MHC class I antigen; antigen presenting cell; blood transfusion; cytotoxic T lymphocyte; disease /disorder model; erythrocytes; flow cytometry; gene targeting; genetically modified animals; helper T lymphocyte; human tissue; immune tolerance /unresponsiveness; isoantibody; isoantigen; laboratory mouse; leukocyte activation /transformation; leukocyte transfusion; platelet transfusion

Transfusion of blood products has been shown to impact a number of the recipient immune responses. The immunological consequences of transfusion include the production of alloantibodies, increased incidence of bacterial infection, increased relapse rates for at least some kinds of tumors, transfusion-associated graft-versus-host disease, increased survival of organ allografts, induction of anti-leukemic responses and reversal of some cases of spontaneous recurrent abortions. Although donor blood and recipient have been matched for blood group antigens, they are not routinely typed for HLA antigens. Thus in almost all cases, the transfusion results in the introduction of alloantigens to the recipients. The goal of the studies is to define the mechanisms regulating recipient immune responses to alloantigen in order to understand how transfusion can influence immune responses and how to best regulate these responses. One approach to study the recipient responses to alloantigen is to study the responses which are responsible for the elimination of the allogeneic donor cells. Recipient CD8+ and B cells are responsible for the elimination of allogeneic donor cells in a murine model sytem. Optimal responses by these cells requires help from CD4+ cells. The most rapid recipient responses were in response to activated donor CD4+ cells acting as alloantigen presenting cells. The proposed experiments will examine the relative importance of this novel pathway by comparing the role of donor CD4+ cells and macrophages as antigen presenting cells. These donor cell populations will be compared by measuring the minimum number of each type of donor cell that is required for recipient immune responses, the interactions that are important in activation of recipient effector responses for each type of cell and how the immune responses generated by these cells regulate other immune responses.

输血产品已被证明会影响受者的一些免疫反应。输血的免疫学后果包括产生同种异体抗体，增加细菌感染的发生率，增加至少某些类型肿瘤的复发率，与输血相关的移植物抗宿主病，增加同种器官移植物的存活率，诱导抗白血病反应，并逆转一些自发的复发性流产病例。尽管捐献者和受血者的血型抗原已经匹配，但他们并不是常规的人类白细胞抗原分型。因此，在几乎所有病例中，输血都会导致将同种异体抗原引入受者体内。这些研究的目的是确定调节受者对同种异体抗原的免疫反应的机制，以了解输血如何影响免疫反应以及如何最好地调节这些反应。研究受者对同种异体抗原的反应的一种方法是研究导致同种异体供体细胞消除的反应。在小鼠模型系统中，受者CD8+和B细胞负责消除异基因供体细胞。这些细胞的最佳反应需要CD4+细胞的帮助。最快的受体反应是对激活的供者CD4+细胞作为同种异体抗原提呈细胞的反应。拟议的实验将通过比较捐赠者的CD4+细胞和巨噬细胞作为抗原提呈细胞的作用来检验这一新途径的相对重要性。这些供体细胞群体将通过测量受者免疫反应所需的每种类型供体细胞的最小数量、在激活每种类型细胞的受者效应反应中重要的相互作用以及这些细胞产生的免疫反应如何调节其他免疫反应来进行比较。