CD2-ACTIVATED T CELL LYMPHOKINE PRODUCTION

CD2 激活的 T 细胞淋巴细胞因子的产生

• 批准号: 3081043
• 负责人: SUSAN C GUBA
• 金额: $ 6.44万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3081043
• 关键词: CD antigens; T lymphocyte; antigen receptors; cell population study; enzyme linked immunosorbent assay; genetic library; genetic transcription; genetic translation; hematopoietic stem cells; leukocyte activation /transformation; lymphokines; messenger RNA; molecular cloning; monoclonal antibody; northern blottings; protein biosynthesis

The functional repertoire of activated T lymphocytes is in large part mediated by lymphokine secretion following T cell activation via one of several transmembrane receptors including TCR/CD3 and CD2. While activation via the TCR/CD3 pathway is the basis for antigen specific T cell responses, CD2 mediated activation underlies antigen independent proliferation, including autoimmune T cell activation. In particular, hematopoietic progenitor cell proliferation can be directly regulated by autoregulatory CD2 activated T cells. Generation of a regulatory (suppressive) T lymphocyte subset occurs when normal cycling HLA-- DR+CD58+progenitor cells induce proliferation of autologous CD4+CD2+T cells. Activation of T cells via the CD2 pathway also appears to generate suppressive T cell lymphokines, specifically tumor necrosis factor-alpha (TNFalpha) and to a lesser extent interferon-gamma (INFgamma). Thus study of the CD2 pathway of T cell activation is of paramount importance in understanding regulation of hematopoiesis. To study the hypothesis that suppressive lymphokines regulate stem cell proliferation, the colony stimulating factors (CSFs) and cytokines produced by CD2 activated, and by auto-activated T cells will be identified. Additionally, the T cell subsets which secrete lymphokines in response to alpha/CD2 stimulation will be identified. If preferential gene transcription of specific suppressive cytokines, e.g. TNFAlpha is confirmed, then the T cell specific molecular mechanisms regulating the transcription of the TNFAlpha gene will be characterized. This research is important in expanding our understanding of autoregulatory hematopoietic homeostasis, receptor-specific T cell activation, and in characterizing bone marrow transplant engraftment.

活化的 T 淋巴细胞的功能大部分是 由 T 细胞激活后淋巴因子分泌介导，通过以下之一 多种跨膜受体，包括 TCR/CD3 和 CD2。 尽管 通过 TCR/CD3 途径激活是抗原特异性 T 细胞的基础 反应，CD2 介导的激活是抗原非依赖性的基础 增殖，包括自身免疫 T 细胞激活。 尤其， 造血祖细胞增殖可直接调控 自我调节 CD2 激活 T 细胞。 监管的产生 （抑制性）T 淋巴细胞亚群发生在 HLA 正常循环时—— DR+CD58+祖细胞诱导自体CD4+CD2+T增殖 细胞。 通过 CD2 途径激活 T 细胞似乎也会产生 抑制性 T 细胞淋巴因子，特别是肿瘤坏死因子-α （TNFα）和较小程度的干扰素-γ（INFγ）。从而学习 T 细胞激活的 CD2 途径的研究至关重要 了解造血的调节。 研究以下假设 抑制性淋巴因子调节干细胞增殖，集落 CD2 激活产生的刺激因子 (CSF) 和细胞因子，以及 自动激活的 T 细胞将被识别。 此外，T 细胞 响应 α/CD2 刺激而分泌淋巴因子的亚群 被识别。 如果特异性抑制基因优先转录 细胞因子，例如TNFAlpha确定了，那么T细胞特异性分子 TNFα基因转录的调节机制 特点。 这项研究对于扩大我们的理解很重要 自身调节造血稳态、受体特异性 T 细胞 激活，以及表征骨髓移植植入。