MYCOBACTERIUM AVIUM-INTRACELLULARE INFECTIONS AND AIDS

该项目的目标是确定以下机制或因素 能有效激活巨噬细胞(Mphis)，杀死或抑制其生长 细胞内分枝杆菌(MAI)。MAI是一种分枝杆菌 感染Mphis导致免疫功能低下的播散性疾病 艾滋病和毛细胞白血病(HCL)患者等个人。我们 将确定MAI感染是否改变了Mphi的激活 巨噬细胞活化标志物人类白细胞抗原-DR和重链的表达 细胞色素B和产生的单因子肿瘤坏死因子-α，白介素1-β， 和IL-6，重要的炎症介质。我们将调查是否 肿瘤坏死因子-α和白介素6在防御急性心肌梗死和脑梗塞中发挥核心作用 多催化清道夫蛋白水解酶的存在是否是必要的 麦毒感染的Mphis生存的先决条件。我们还将检查 细胞因子MIF、M-CSF、GM-CSF、IL-4和TGF-β对血管内皮细胞生长的影响 它们激活Mphis以抑制生长和杀死MAI的能力。级别 伴有和不伴有AIDS和HCL的患者外周血中的γ-T细胞 现有的MAI感染将与正常捐赠者的水平进行比较。T 对分枝杆菌抗原有反应的细胞克隆将被开发出来。这些T 然后细胞和它们的淋巴因子将与感染麦毒的Mphis一起培养。 以确定它们是否对MAI生长有抑制作用。相关性 人类白细胞抗原分型、肿瘤坏死因子的产生与Mphis的MAI生长之间的关系将被尝试。 艾滋病和慢性淋巴细胞性白血病患者的临床表现及HIV特异性蛋白对MAI的影响 我们将考察增长情况。 这些研究旨在开发或确定激活方案 这使得感染MAI的Mphis能够控制MAI的细胞内生长。 我们最近发现，MIF是一种具有多种功能的T细胞淋巴因子 对Mphis的激活作用几乎完全抑制MAI的生长(99%) 梅菲斯。我们认为使用MIF的治疗方案可能会导致 特定的Mphi激活和随后的MAI杀死，并将具有 在晚期MAI感染控制中具有较大的实用价值 感染艾滋病毒的人。

The goals of this project are to determine the mechanisms or factors that can effectively activate macrophages (Mphis) to kill or inhibit the growth of Mycobacterium avium-intracellulare (MAI). MAI is a mycobacterium infecting Mphis which causes disseminated disease in immunocompromised individuals such as patients with AIDS and hairy cell leukemia (HCL). We will determine whether MAI infection alters Mphi activation as measured by the expression of the macrophage activation markers HLA-DR and heavy chain of cytochrome B and the production of the monokines TNF-alpha, IL-1beta, and IL-6, important mediators of inflammation. We will investigate whether TNF-alpha and IL-6 play a central role in the defense against MAI and whether the presence of multicatalytic scavenger proteases is a necessary prerequisite for the survival of MAI-infected Mphis. We will also examine the effects of the cytokines MIF, M-CSF, GM-CSF, IL-4, and TGF-beta on their ability to activate Mphis to inhibit growth and kill MAI. Levels of circulating gammabeta T cells in AIDS and HCL patients with and without existing MAI infections will be compared to levels in normal donors. T cell clones reactive to mycobacterial antigens will be developed. These T cells and their lymphokines will then be cultured with MAI-infected Mphis to determine if they have an inhibitory effect on MAI growth. Correlation between HLA type, TNF production and MAI growth in Mphis will be attempted in AIDS and HCL patients and the effects of specific HIV proteins on MAI growth will be examined. These studies are designed to develop or identify an activation scheme which enables MAI-infected Mphis to control intracellular growth of MAI. We have recently found that MIF, a T cell lymphokine with various activating effects on Mphis, almost totally inhibits MAI growth (99%) in Mphis. We think that a treatment regimen involving MIF may lead to specific Mphi activation and subsequent MAI killing and will have considerable practical value in the control of MAI infections in late stage HIV-infected individuals.