CD1d-restricted T cells and anti-phospholipid antibodies

CD1d 限制性 T 细胞和抗磷脂抗体

• 批准号: 6557845
• 负责人: Jenny E. Gumperz
• 金额: $ 25.95万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-19 至 2003-11-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6557845
• 关键词: B lymphocyte; CD1 molecule; T lymphocyte; antiantibody; antigen antibody reaction; antigen presentation; autoantibody; blood chemistry; cardiovascular disorder; chimeric proteins; chronic spontaneous abortion; clinical research; clone cells; density gradient ultracentrifugation; enzyme linked immunosorbent assay; flow cytometry; fluorescent dye /probe; human subject; leukocyte activation /transformation; leukocyte count; pathologic process; phospholipids; systemic lupus erythematosus

DESCRIPTION (provided by applicant): Anti-phospholipid antibodies are a type of autoantibody associated with significant cardiovascular pathology, stroke, and recurrent miscarriages. It is not known how these antibodies arise, or whether T cells are involved in their generation. CD1d-restricted T cells are a novel population of T lymphocytes that recognize lipid and glycolipid antigens, including in some cases phospholipids. CD1d molecules are expressed on antigen presenting cells, including B cells. This proposal investigates the hypothesis that anti-phospholipid antibody production by B cells could be regulated by CD1d-restricted T cells in an antigen specific manner. The analysis focuses on whether the presence of elevated levels of pathogenic anti-phospholipid antibodies correlates with changes in the numbers, activation states, functions, or antigen specificities of CD1d-restricted T cells. This will be assessed in the following specific aims: i) flow cytometric analysis will be performed using lipid antigen loaded CD1d tetramers to detect and analyze the functional properties of CD1d-restricted T cells from peripheral blood of patients with anti-phospholipid antibodies compared to control donors; ii) binding of different phospholipids to CD1d molecules will be analyzed using CD1d-Fc fusion proteins and fluorescent or radiolabeled phospholipids; iii) CD1d-restricted T cell clones will be derived from patients with anti-phospholipid antibodies and control donors, and used to investigate reactivity to individual phospholipids, and to test recognition of anti-phospholipid antibody producing B cells. This investigation will provide new insight into the role of autoreactive T cells in the generation of autoantibodies, and may provide new diagnostic and therapeutic approaches for conditions associated with pathogenic anti-phospholipid antibodies.

描述（由申请人提供）：抗磷脂抗体是一种与大量心血管病理，中风和反复流产相关的自身抗体。尚不清楚这些抗体是如何产生的，或者T细胞是否参与了它们的一代。 CD1D限制的T细胞是识别脂质和糖脂抗原的新型T淋巴细胞种群，包括在某些情况下磷脂。 CD1D分子在包括B细胞在内的抗原呈递细胞上表达。该提案调查了以下假设：B细胞可以以抗原特异性方式调节B细胞的抗磷脂抗体。该分析的重点是致病性抗磷脂抗体水平升高是否与CD1D限制T细胞的数量，激活状态，功能或抗原特异性的变化有关。这将在以下具体目的中进行评估：i）将使用脂质抗原加载的CD1D四聚体进行流式细胞仪分析，以检测和分析来自抗磷脂抗体患者外周血的CD1D限制T细胞的功能特性，与对照供体相比； ii）将使用CD1D-FC融合蛋白以及荧光或放射性标记的磷脂的结合将不同的磷脂与CD1D分子结合； iii）CD1D限制的T细胞克隆将来自具有抗磷脂抗体和对照供体的患者，并用于研究对单个磷脂的反应性，并测试对产生B细胞的抗磷脂抗体的识别。这项研究将为自动反应性T细胞在自身抗体生成中的作用提供新的见解，并可能为与致病性抗磷脂抗体相关的疾病提供新的诊断和治疗方法。