PRECLINICAL ANIMAL MODEL TO ASSESS THE SAFETY OF RETROVIRALLY RESISTANT CELLS

评估逆转录病毒抗性细胞安全性的临床前动物模型

• 批准号: 6161320
• 负责人: A S ROSENBERG
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6161320
• 关键词: Retroviridae disease; cell population study; cell sorting; cell transplantation; cytotoxic T lymphocyte; disease /disorder model; disease /disorder proneness /risk; genetic strain; genotype; hematopoietic tissue transplantation; immune tolerance /unresponsiveness; immunity; laboratory mouse; microorganism immunology; model design /development; murine AIDSs; nonhuman therapy evaluation; tissue mosaicism

Transplantation of retrovirally resistant cells has been proposed as a therapeutic modality to treat HIV infected patients. We developed an animal model in which to explore the safety of administration of retrovirally resistant cells into susceptible animals. Using a murine model of acquired immunodeficiency induced by retroviruses, we established that there is a critical balance between susceptible and resistant lymphoid cells that determines whether the animals succumb to disease, or achieve long term resistance in that only animals containing >50% resistant cells were completely protected from disease. Critically, no changes in tropism of the infective retrovirus were detected during the course of the study . To assess the anti-retroviral mechanisms that confer resistance in this model, we have constructed animals in which the resistant cell population is deficient in receptors for IFN-gamma and are pursuing construction of resistant strain mice deficient in perforin, required for some aspects of cell mediated cytotoxicity. The latter mice have been infected and results pending. This program directly supports the mission of the Center by creating an animal model to allow us to anticipate the safety and potential efficacy of therapeutic modalities involving tranplantation of lymphoid populations resistant to HIV into HIV infected humans. One such protocol involving transplant of baboon bone marrow is already in progress.

逆转录病毒抗性细胞的移植已被提出作为一种治疗方法