HEMATOPOIESIS IN AIDS

这个项目是基于这样一种假设，即 获得性免疫缺陷综合征(AIDS)的贫血和粒细胞减少。 艾滋病相关复合体(ARC)，以及这些疾病的治疗，可以 涉及异常的造血祖细胞，或者 祖细胞间的异常相互作用与人类免疫缺陷 病毒(HIV)感染的造血辅助细胞(即T细胞和 单核细胞)或两者都有。具体目的是：1)确定是否使用了药物 在治疗HIV感染的过程中调节增殖和 红系和髓系祖细胞体外分化的研究 确定造血生长因子是否可以中和抑制 抗病毒药物的造血作用；3)体内药物效果的测定 无症状HIV患者的体外造血治疗 感染、艾滋病和ARC；以及4)确定患者的造血功能受损 HIV感染是由于红系和髓系功能异常所致 HIV感染导致祖细胞或调节功能受损 辅助细胞(T细胞和单核细胞)，或两者兼而有之。在医院使用的药物 艾滋病的治疗和ARC和造血生长因子将增加 对正常成人骨髓和/或外周血的培养 单独和联合感染艾滋病毒的患者。其影响将是 通过计数祖细胞来源的集落进行评估。剂量反应 将为每种被测试的药物生成曲线。以确定药物是否 对早期祖细胞或较晚成熟的造血细胞发挥作用 细胞，单个核细胞(MNC)将与药物预先‘脉冲’培养 至培养，否则将在培养期间连续添加药物。 以确定药物是否直接作用于祖细胞和/或通过 辅助细胞，药物将添加到单核细胞耗尽的单核细胞，T- 细胞、T细胞亚群或其组合。的协同效应 药物将通过将药物组合添加到培养物中进行测试。 参与临床试验的HIV感染者的祖细胞 将在治疗前、治疗中和治疗后进行培养以评估 体内处理祖细胞和辅助细胞的效果。至 确定感染HIV的T细胞和单核细胞是否可以正常运行 辅助细胞功能，MNC将耗尽这些细胞和 单独培养和与附加辅助细胞联合培养。这个 这些研究的最终目标是更好地理解 艾滋病和ARC的贫血和粒细胞减少的病因，以及 建议适当的治疗方法。

This project is based on the hypothesis that the pathophysiology of anemia and granulocytopenia in acquired immunodeficiency syndrome (AIDS). AIDS related complex (ARC), and the treatment of these diseases, can involve abnormal hematopoietic progenitor cells, or alternatively an abnormal interaction between progenitor cells and human immunodeficiency virus(HIV) infected hematopoietic accessory cells (i.e., T cells and monocytes) or both. The specific aims are to; 1) determine if drugs used in the treatment of HIV infection modulate proliferation and differentiation of erythroid and myeloid progenitor cells in vitro; 2) determine if hematopoietic growth factors can counteract inhibition of hematopoiesis by antiviral drugs; 3) determine the effect of in vivo drug therapy on in vitro hematopoiesis in patients with asymptomatic HIV infection, AIDS, and ARC; and 4) determine if impaired hematopoiesis in HIV infection is due to abnormally functioning erythroid and myeloid progenitor cells or impaired regulatory functions by HIV infected accessory cells (T-cells and monocytes), or both. Drugs used in the treatment of AIDS and ARC and hematopoietic growth factors will be added to cultures of bone marrow and/or peripheral blood of normal adults and HIV infected patients alone and in combination. The effects will be evaluated by counting progenitor cell derived colonies. Dose response curves will be generated for each drug tested. To determine if drugs exert their effects on early progenitors or later maturing hemopoietic cells, mononuclear cells (MNC) will be 'pulse' incubated with drugs prior to culture, or drugs will be added serially during the cultured period. To determine if drugs act directly on progenitor cells and/or via accessory cells, drugs will be added to MNC depleted of monocytes, T- cells, T-cell subsets, or combinations thereof. Synergistic effects of drug will be tested by adding combinations of drugs to cultures. Progenitor cells HIV infected patients participating in clinical trails will be cultured prior to, during and after treatment to assess the effect of in vivo treatment of progenitor and accessory cells. To determine if HIV infected T-cells and monocytes can perform normal accessory cell functions, MNC will be depleted of these cells and cultured alone and in combination with added accessory cells. The ultimate goal of these studies is to develop a better understanding of the etiology of anemia and granulocytopenia in AIDS and ARC, and to suggest appropriate therapies.