ROLE OF CD4 T CELL SUBSETS IN MAIDS

我们建议对MAIDS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发生严重疾病 包括免疫缺陷、淋巴增生、频繁发育 淋巴瘤和死亡 疾病的一个方面是早期改变， CD 4亚群的T细胞，这表明他们已经经历了一种 多克隆激活，这导致了它们的增殖，但结果是， 他们的免疫缺陷。 因为需要CD 4 T细胞亚群 对于疾病的开始和进展，很可能是这些 CD 4 T细胞的变化在疾病过程中起关键作用。 我们计划鉴定出接受免疫调节的CD 4 T细胞亚群。 表型转换和确定疾病所需的。 我们 将检查初始和记忆CD 4 T细胞亚群的贡献， 评估反应是否具有抗原或超抗原的标志 诱导性无反应性。 克隆、表达的缺陷型病毒gp-60多蛋白将 直接检测超抗原活性。 我们将评估 病毒在某种程度上扰乱了胸腺的选择， 行动仅限于外围。 我们还将调查 型携带缺陷病毒，并合成病毒产物。 我们将 评估响应的T细胞的频率，以及它们是否 少量或大量扩散。 我们还将测定淋巴因子 在疾病期间产生，识别正在合成的细胞类型 并研究是否阻断选定的淋巴因子的作用， 干扰疾病。 这些研究将在体内进行， 也是在我们正在尝试开发的体外模型中。 烘干机进出 我们希望通过体外模型来识别参与的实际细胞相互作用， MAIDS中的CD 4转化。 我们希望这些结果将揭示关于 在这种特殊的逆转录病毒介导的宿主-病毒相互作用机制中， 疾病 由于艾滋病和艾滋病之间有许多相似之处， 研究结果还将为研究机制提供更全面的见解， 其通常可能参与免疫缺陷的诱导 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.