HEMATOPOIESIS IN AIDS

这个项目是基于这样一个假设， 获得性免疫缺陷综合征（AIDS）中的贫血和粒细胞减少症。 艾滋病相关综合征（ARC），以及这些疾病的治疗， 涉及异常造血祖细胞，或者 祖细胞与人类免疫缺陷的异常相互作用 病毒（HIV）感染的造血辅助细胞（即，T细胞和 单核细胞）或两者。具体目标是：1）确定是否使用药物 在HIV感染的治疗中调节增殖， 体外红系和髓系祖细胞的分化; 2） 确定造血生长因子是否可以抵消抑制 抗病毒药物的造血作用; 3）确定体内药物的作用 无症状HIV感染者体外造血治疗 感染、AIDS和ARC;以及4）确定是否存在造血功能受损， 艾滋病毒感染是由于红细胞和髓细胞功能异常 祖细胞或受损的调节功能的HIV感染 辅助细胞（T细胞和单核细胞）或两者。使用的药物 治疗艾滋病和ARC和造血生长因子将增加 正常成人的骨髓和/或外周血培养物， HIV感染者单独和联合使用。其影响将是 通过计数祖细胞衍生的集落来评价。剂量反应 将为每种测试药物生成曲线。为了确定药物是否 对早期祖细胞或晚成熟造血细胞发挥作用 细胞，单核细胞（MNC）将与药物一起“脉冲”孵育， 或在培养期间连续加入药物。 为了确定药物是否直接作用于祖细胞和/或通过 辅助细胞，药物将被添加到耗尽单核细胞、T- 细胞、T细胞亚群或其组合。的协同效应 将通过向培养物中加入药物组合来测试药物。 参与临床试验的HIV感染者的祖细胞 将在治疗前、治疗期间和治疗后进行培养， 体内处理祖细胞和辅助细胞的效果。到 确定HIV感染的T细胞和单核细胞是否可以正常 辅助细胞功能，MNC将耗尽这些细胞， 单独培养和与添加的辅助细胞组合培养。的 这些研究的最终目标是更好地了解 艾滋病和ARC患者贫血和粒细胞减少症的病因， 建议适当的治疗。

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.