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: 2133832
• 负责人: SUSAN C GUBA
• 金额: $ 6.94万
• 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/2133832
• 关键词: CD2 molecule; 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; nucleic acid sequence; 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淋巴细胞的功能库在很大程度上是 通过T细胞活化后的淋巴因子分泌介导， 几种跨膜受体，包括TCR/CD 3和CD 2。 而 通过TCR/CD 3途径的活化是抗原特异性T细胞免疫的基础。 CD 2介导的活化是抗原非依赖性的 增殖，包括自身免疫T细胞活化。 特别是， 造血祖细胞增殖可以通过以下方式直接调节 自身调节性CD 2活化T细胞。 生成监管 （抑制性）T淋巴细胞亚群发生时，正常循环HLA- DR+ CD 58+祖细胞诱导自体CD 4 + CD 2 +T细胞增殖 细胞 通过CD 2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 （TNF α）和较小程度的干扰素-γ（INF γ）。因此，研究 T细胞活化的CD 2途径在 了解造血的调节。 为了研究这个假设， 抑制性淋巴因子调节干细胞增殖，殖民地 刺激因子（CSF）和细胞因子产生的CD 2活化， 将鉴定自活化的T细胞。 此外，T细胞 应答α/CD 2刺激而分泌淋巴因子的亚群将 被识别。 如果特异性抑制基因的优先转录 细胞因子，例如TNF α被确认，则T细胞特异性分子 调节TNF α基因转录的机制将是 表征了 这项研究对于扩大我们对 自身调节造血稳态，受体特异性T细胞 活化和表征骨髓移植植入。