ROLE OF CD4 T CELL SUBSETS IN MAIDS

我们建议对女佣的诱导机制进行详细的研究。B6 接种BM-5逆转录病毒混合物的小鼠患上严重疾病 包括免疫缺陷，淋巴增殖，频繁的发展 淋巴瘤和死亡。疾病的一个方面是早期的改变 T细胞的CD4亚群，表明它们经历了一种 引起它们增殖的多克隆激活，但结果是 在他们的免疫缺陷方面。因为CD4T细胞亚群是必需的 对于疾病的启动和发展，很可能是这些 CD4T细胞的变化在疾病过程中起着关键作用。 我们计划确定CD4T细胞亚群(S)经历 表型转换，并确定疾病所需的。我们 将研究幼稚和记忆性CD4T细胞亚群的贡献 评估反应是否具有抗原或超抗原的特征 诱导性无能。克隆、表达缺陷病毒GP-60多蛋白将 直接检测超抗原活性。我们将评估是否 病毒以某种方式扰乱了胸腺的选择，或者是 行动仅限于外围国家。我们还将调查哪些细胞 不同类型的人携带有缺陷的病毒，并合成病毒产物。我们会 评估T细胞的应答频率以及它们是否 繁殖得很少或很多。我们还将测定淋巴因子 病程中产生，鉴定合成的细胞类型(S) 并研究是否阻断选定的淋巴因子的作用 干扰疾病。这些研究将在体内和 也是在我们试图开发的体外模型中。在里面 我们希望通过体外模型来确定参与其中的实际细胞相互作用 女仆体内的CD_4转化率。 我们预计，这些结果将揭示关于 这种逆转录病毒介导的宿主-病毒相互作用机制 疾病。由于女佣和艾滋病之间有许多相似之处，我们预计 这一结果还将提供对该机制的更全面的了解 它可能通常与免疫缺陷的诱导有关 疾病。

We propose a detailed study of the mechanism of induction of MAIDS. B6 mice inoculated with the BM-5 retrovirus mixture develop a severe disease which includes immunodeficiency, lympho-proliferation, frequent development of lymphoma and death. One facet of disease is an early alteration in the CD4 subset of T cells which suggests that they have undergone a kind of polyclonal activation which has caused their proliferation, but resulted as well in their immunodeficiency. Because the CD4 T cell subset is required for the disease to be initiated and to progress, it is likely that these changes in CD4 T cells play a key role in the disease process. We plan to identify the subset(s) of CD4 T cells that undergo the phenotypic conversion and identify that which is required for disease. We will examine the contribution of naive and memory CD4 T cell subsets and evaluate whether the response has the hallmarks of antigen or superantigen induced anergy. Cloned, expressed defective virus gp-60 polyproteins will be directly tested for superantigen activity. We will evaluate whether the virus somehow perturbs selection in the thymus or whether the mechanism of action is restricted to the periphery. We will also investigate what cell types harbor defective virus, and synthesize viral products. We will evaluate the frequency of T cells which respond and whether they proliferate a little or a lot. We will also determine the lymphokines produced during disease, identity the cell type(s) that is synthesizing them and investigate whether blocking the action of selected lymphokines interferes with disease. These studies will be pursued both in vivo and also in an in vitro model that we are attempting to develop. In the in vitro model we hope to identity the actual cell interactions involved in CD4 conversion in MAIDS. We expect that these results will reveal important principles about the mechanism of host-virus interaction in this particular retrovirus mediated disease. Since there are many parallels between MAIDS and AIDS, we expect that the results will also provide more general insight into the mechanism which may be generally involved in the induction of immunodeficiency disease.