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T细胞克隆及其产物:细胞内细菌感染免疫预防和免疫治疗的实验线索?

T cell clones and their products: experimental clues for the immunoprophylaxis and immunotherapy of intracellular bacterial infections?

作者信息

Kaufmann S H

出版信息

Infection. 1985;13 Suppl 2:S177-83. doi: 10.1007/BF01644426.

Abstract

In this paper experimental models utilizing murine T cell clones specific for the intracellular bacterium Listeria monocytogenes are described and some matters of possible relevance to the development of novel immunological strategies against intracellular bacterial infections discussed. Improved vaccines against intracellular bacteria should be selected for their expression of a maximum amount of immunoprotective epitopes and their lack of immunosuppressive epitopes. Analysis of these epitopes may be accomplished with T cell clones of known biological activities. Alternatively, active vaccination in the absence of the etiological agent using idiotypic or clonotypic antibodies may be considered. Improved vaccines against intracellular bacteria must also have the capacity to induce strong T cell responses. Intensified efforts should therefore be undertaken to overcome the current lack of medically acceptable adjuvants for the stimulation of cellular immunity. Once adjuvants as well as defined antigens have become available, the construction of a novel generation of highly effective vaccines should become feasible. In experimental models, T cell clones which confer antibacterial protection have been established. However, these T cell clones expressed low in vivo activity, most probably due to the acquisition of an aberrant migration pattern. Thus, the application of T cell clones for adoptive vaccination against intracellular bacteria in clinical medicine appears to be premature. The observation that lymphokines could protect mice against listeriosis indicates that immunotherapy of intracellular bacterial infections with lymphokines may be a realistic goal in the near future.

摘要

本文描述了利用针对胞内细菌单核细胞增生李斯特菌的鼠T细胞克隆的实验模型,并讨论了一些可能与开发针对胞内细菌感染的新型免疫策略相关的问题。针对胞内细菌的改良疫苗应根据其表达最大量免疫保护表位以及缺乏免疫抑制表位来选择。这些表位的分析可以用已知生物学活性的T细胞克隆来完成。或者,可以考虑在没有病原体的情况下使用独特型或克隆型抗体进行主动免疫。针对胞内细菌的改良疫苗还必须具备诱导强烈T细胞反应的能力。因此,应该加大力度克服目前缺乏可用于刺激细胞免疫的医学上可接受的佐剂这一问题。一旦有了佐剂以及明确的抗原,新一代高效疫苗的构建应该会变得可行。在实验模型中,已经建立了具有抗菌保护作用的T细胞克隆。然而,这些T细胞克隆在体内活性较低,很可能是由于获得了异常的迁移模式。因此,在临床医学中应用T细胞克隆进行针对胞内细菌的过继免疫似乎还为时过早。细胞因子能够保护小鼠免受李斯特菌病感染这一观察结果表明,用细胞因子对胞内细菌感染进行免疫治疗在不久的将来可能是一个现实的目标。

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