MYCOBACTERIUM AVIUM-INTRACELLULARE INFECTIONS AND AIDS

本项目的目标是确定 能有效激活巨噬细胞（Mphis）杀死或抑制生长 鸟胞内分枝杆菌（Mycobacterium avium-intracellulare，MAI） MAI是一种分枝杆菌 感染Mphis会导致免疫功能低下的传播性疾病 艾滋病和毛细胞白血病（HCL）患者。 我们 将确定MAI感染是否改变Mphi激活， 巨噬细胞活化标志物HLA-DR和重链的表达 细胞色素B和单核因子TNF-α，IL-1 β， 和IL-6，炎症的重要介质。 我们将调查是否 TNF-α和IL-6在抗MAI的防御中起核心作用， 多催化性清道夫蛋白酶的存在是否是必需的 这是感染MAI的Mphis存活的先决条件。 我们亦会研究 细胞因子MIF、M-CSF、GM-CSF、IL-4和TGF-β对 它们激活Mphis以抑制生长并杀死MAI的能力。 水平 艾滋病和HCL患者的循环γ-T细胞 现有的MAI感染将与正常供体的水平进行比较。 不 将开发对分枝杆菌抗原有反应性的细胞克隆。 这些T 然后将细胞及其淋巴因子与MAI感染的Mphis一起培养， 以确定它们是否对MAI生长具有抑制作用。 相关性 将尝试在Mphis中的HLA类型、TNF产生和MAI生长之间进行比较 在艾滋病和HCL患者中的作用以及特定HIV蛋白对MAI的影响 增长将受到考验。 这些研究旨在开发或确定一种激活方案 这使得MAI感染的Mphis能够控制MAI的细胞内生长。 我们最近发现，MIF，一种T细胞淋巴因子， 激活Mphis的作用，几乎完全抑制MAI生长（99%）， Mphis 我们认为，涉及MIF的治疗方案可能会导致 特异性Mphi激活和随后的MAI杀伤， 对控制MAI后期感染有一定的实用价值 艾滋病毒感染者。

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.