Wisseman C L, Waddell A
J Exp Med. 1983 Jun 1;157(6):1780-93. doi: 10.1084/jem.157.6.1780.
Unique features of the primary site of rickettsial replication in typhus fevers, i.e., within the endothelial cells of small blood vessels in tissues, suggest that effector mechanisms, other than those dependent on phagocytosis by activated macrophages with enhanced microbicidal properties, most likely are necessary to explain the cell-mediated immune control of intracellular rickettsial replication in these sites. Theoretically, such mechanisms might involve contact between infected endothelial cells and activated T lymphocyte subpopulations or macrophages or immunologically induced soluble factors or lymphokines. Support for the existence of at least one of these alternative effector mechanisms is presented here for Rickettsia prowazekii. Cultures of human blood leukocytes, upon immunologically specific stimulation with R. prowazekii antigen or nonspecific stimulation with the mitogen phytohemagglutinin, produce soluble factor(s) in the supernatant fluid which, in culture, have (a) an intracellular antirickettsial action on R. prowazekii-infected human endothelial cells, fibroblasts, and macrophages, and (b) a specific cytolytic action on R. prowazekii-infected, but not uninfected bystander, human fibroblasts. Neither action is demonstrable in R. prowazekii-infected chicken embryo fibroblasts. The factor(s) has no direct antimicrobial action on extracellular rickettsiae and is inactivated by heating at 56 degree C for 1 h or by acid treatment at pH 2. Expression of the antirickettsial action requires new host cell messenger transcription and protein synthesis, whereas the cytolytic action does not. The circumstances of production and action and the properties of the factor(s) responsible for the intracellular antirickettsial, and perhaps also the cytolytic action are consistent with those of immune interferon (IFN-gamma).
斑疹伤寒立克次体复制的主要部位具有独特特征，即在组织中小血管的内皮细胞内，这表明除了依赖具有增强杀菌特性的活化巨噬细胞吞噬作用的效应机制外，很可能还需要其他效应机制来解释这些部位细胞介导的对细胞内立克次体复制的免疫控制。从理论上讲，此类机制可能涉及受感染的内皮细胞与活化的T淋巴细胞亚群或巨噬细胞之间的接触，或免疫诱导的可溶性因子或淋巴因子。本文提供了有关普氏立克次体存在至少一种这些替代效应机制的证据。人血白细胞培养物在受到普氏立克次体抗原的免疫特异性刺激或有丝分裂原植物血凝素的非特异性刺激后，会在上清液中产生可溶性因子，该因子在培养中具有以下作用：（a）对感染普氏立克次体的人内皮细胞、成纤维细胞和巨噬细胞具有细胞内抗立克次体作用；（b）对感染普氏立克次体但未感染的旁观者人成纤维细胞具有特异性细胞溶解作用。在感染普氏立克次体的鸡胚成纤维细胞中未发现这两种作用。该因子对细胞外立克次体没有直接抗菌作用，在56℃加热1小时或在pH 2下进行酸处理会使其失活。抗立克次体作用的表达需要新的宿主细胞信使转录和蛋白质合成，而细胞溶解作用则不需要。负责细胞内抗立克次体作用以及可能还有细胞溶解作用的因子的产生和作用情况及其特性与免疫干扰素（IFN-γ）一致。
