EXPRESSION OF THE OX40/GP34 SYSTEM IN CUTANEOUS GRAFT VERSUS HOST DISEASE

OX40/GP34 系统在皮肤移植物抗宿主疾病中的表达

• 批准号: 6235808
• 负责人: ROBERT A SWERLICK
• 金额: $ 5.56万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-01 至 1998-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6235808
• 关键词: T lymphocyte; apoptosis; cell adhesion; cell differentiation; cell growth regulation; chimeric proteins; clinical research; cytokine; graft versus host disease; human subject; immunocytochemistry; laboratory mouse; lymphocyte proliferation; neurotrophic factors; northern blottings; polymerase chain reaction; receptor; receptor binding; skin; tissue /cell culture; tumor necrosis factor alpha

The OX40 receptor and gp34 ligand system is a recently characterized receptor/ligand pair. First identified on activated rat CD4+ cells, OX40 has been demonstrated to be a 50kD cell surface glycoprotein whose expression in human blood seems to be limited to activated T-cells. Human OX40 is a member of the nerve growth factor receptor/tumor necrosis factor family whose members also include fas/APO-1, CD40, CD27, CD30, and 4-1BB/ILA antigens. These molecules are involved with regulation of cell growth, differentiation and apoptosis. Gp34 was recently discovered to be the ligand for human OX40. It is a type II membrane glycoprotein expressed on HTLV-1 infected T-cell lines. Gp34 is also expressed on EBV-infected B-cells, activated peripheral circulating B-cells, and it appears to mediate binding of activated T- cells to human dermal microvascular endothelial cells. The exact function of this receptor/ligand pair is unclear. However, recent studies have shown that in addition to cell adhesion, OX40/gp34 crosslinking results in propagation of T-cell proliferation, B-cell proliferation and differentiation into antibody producing plasma cells, and an alteration in cytokine secretion. The goal of this proposed investigation is to characterize the distribution of this receptor/ligand pair in murine and human skin and to determine its role in the pathogenesis of cutaneous graft versus host disease (GvHD).

OX 40受体和gp 34配体系统是最近表征的 受体/配体对。 首先在活化的大鼠CD 4+细胞上发现， OX 40已被证明是一种50 kD的细胞表面糖蛋白， 在人血液中的表达似乎限于活化的T细胞。 人OX 40是神经生长因子受体/肿瘤的成员 坏死因子家族，其成员还包括fas/APO-1，CD 40，CD 27， CD 30和4-1BB/ILA抗原。 这些分子与 调节细胞生长、分化和凋亡。 GP 34是 最近发现是人OX 40的配体。 这是第二型 在HTLV-1感染的T细胞系上表达的膜糖蛋白。 Gp34 也表达于EBV感染的B细胞、活化的外周血淋巴细胞、 循环B细胞，它似乎介导激活的T细胞的结合， 人真皮微血管内皮细胞。 的确切 这种受体/配体对的功能尚不清楚。 但最近的 研究表明，除了细胞粘附，OX 40/gp 34 交联导致T细胞增殖、B细胞 增殖并分化为产生抗体的浆细胞， 以及细胞因子分泌的改变。 这一提议的目的是 调查是为了描述这种分布 受体/配体对小鼠和人皮肤，并确定其作用 皮肤移植物抗宿主病（GvHD）的发病机制。