REGULATION OF THYMOPOIESIS IN HIV1 DISEASE

HIV1 疾病中胸腺生成的调节

• 批准号: 6631605
• 负责人: LAURA A NAPOLITANO
• 金额: $ 11.88万
• 依托单位: J. DAVID GLADSTONE INSTITUTES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2004-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6631605
• 关键词: CD antigens; HIV infections; SCID mouse; apoptosis; cell growth regulation; clinical research; growth factor; histogenesis; human subject; pathologic process; thymus; tissue /cell culture

HIV-1 infection, bone marrow transplantation, and intensive chemotherapy are states of profound immune depression marked by peripheral T- lymphocyte depletion and deficiencies in cell-mediated immunity. Full recovery of the immune system requires complete reconstitution of the T cell repertoire. The thymus gland is the primary site of T cell development. Consequently, the state of thymic function in an immunodeficient individual may be a pivotal factor in immune reconstitution. The normal pattern of age-dependent thymic involution is apparently reversed in some pathologic states. Thymic enlargement has been observed in some adults with Grave's disease, after correction of Cushing's syndrome, or after recovery from chemotherapy. This implies that thymic reserve persists into adulthood and can be summoned. Recent data from our laboratory demonstrate abundant thymic tissue in a surprisingly large fraction of HIV-1+ adults. The presence of abundant thymus is significantly associated with increased total CD4+ cells and increased naive CD4+ T cells. We propose that HIV-1 mediated destruction of peripheral T cells induces production of a serum factor which feeds back upon the thymus to upregulate thymopoiesis. Our finding of abundant thymus and increased naive CD4+ cells in some adults with HIV-1 infection provides us with an ideal opportunity to examine regulators of thymopoiesis in HIV-1 disease. The specific aims of this proposal are: (1) To optimize an in vitro assay system to measure regulators or human thymopoiesis; (2) To analyze HIV-1+ human sera for the presence of known and unknown regulators of thymopoiesis, and (3) To determine whether putative positive and/or negative regulators of thymopoiesis are active in vivo using the SCID-hu Thy/Liv mouse model.

HIV-1感染、骨髓移植和强化化疗 是一种严重的免疫抑制状态， 淋巴细胞耗竭和细胞介导的免疫缺陷。 充分 免疫系统的恢复需要完全重建免疫系统。 T细胞库。 胸腺是T细胞的主要场所， 发展 因此，胸腺功能的状态， 免疫缺陷个体可能是免疫缺陷的关键因素 重组 年龄依赖性胸腺退化的正常模式显然是 在某些病理状态下逆转。 胸腺肿大一直是 在一些患有格雷夫斯病的成年人中观察到， 库欣综合征，或化疗后恢复。 这意味 这种胸腺储备会持续到成年期，并且可以被唤起。 我们实验室的最新数据表明， 在HIV-1阳性的成年人中所占的比例之大令人惊讶。 的存在 胸腺丰富与总CD 4+增加显著相关 细胞和增加的初始CD 4 + T细胞。 我们认为HIV-1介导的 外周T细胞的破坏诱导血清因子的产生 反馈到胸腺上以上调胸腺生成。 我们 在一些成人中发现大量胸腺和幼稚CD 4+细胞增加 HIV-1感染者提供了一个理想的机会， HIV-1疾病中的胸腺生成调节因子。 本研究的具体目的是：（1）优化体外培养条件， 测定系统，以测量调节剂或人胸腺生成;（2）分析 HIV-1+人血清中是否存在已知和未知的 （3）确定是否为推定阳性和/或 使用SCID-hu，胸腺生成的负调节因子在体内是活跃的。 Thy/Liv小鼠模型。