Summary
In this paper experimental models utilizing murine T cell clones specific for the intracellular bacteriumListeria 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 lowin 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.
Zusammenfassung
In der vorliegenden Arbeit werden Experimente mit T-Zellklonen von Mäusen, die für das intrazelluläre BakteriumListeria monocytogenes spezifisch sind, beschrieben und einige Aspekte mit Relevanz für die Entwicklung neuer Strategien gegen Infektionen mit intrazellulären Bakterien diskutiert. Gegen intrazelluläre Bakterien gerichtete Vakzinen sollten so ausgewählt werden, daß sie ein Maximum an immunprotektiven und keine immunsuppressiven Epitope besitzen. Die Analyse derartiger Epitope ist durch den Einsatz von T-Zellklonen mit bekannter biologischer Aktivität möglich geworden. Alternativ sollte die Möglichkeit in Betracht gezogen werden, mit Hilfe idiotypischer oder klonotypischer Antikörper, in Abwesenheit des ätiologischen Agens, Schutz hervorzurufen. Vakzinen gegen intrazelluläre Bakterien müssen weiterhin in der Lage sein, eine starke T-Zellantwort hervorzurufen. Da medizinisch akzeptable Adjuvanzien für den Bereich der zellulären Immunität noch nicht zur Verfügung stehen, sollte deren Entwicklung verstärkt angegangen werden. Wenn derartige Adjuvantien sowie definierte Antigene zur Verfügung stehen, könnte gezielt eine neue Generation hochaktiver Vakzinen entwickelt werden. Im Experimentalmodell gelang es, T-Zellklone zu etablieren, die adoptiv Schutz übertragen. Diese T-Zellklone zeigten aber nur eine geringeIn vivo-Aktivität, was in erster Linie auf ein verändertes Migrationsverhalten zurückzuführen sein dürfte. Zur Zeit ist es daher verfrüht, an einen Einsatz von T-Zellklonen in der Medizin zu denken. Durch Gabe von Lymphokinen konnte im Modell der experimentellen Listeriose der Maus antibakterieller Schutz erzielt werden. Eine Immuntherapie intrazellulärer bakterieller Infektionen mit Lymphokinen scheint daher auch in der Medizin in den Bereich des Möglichen zu rücken.
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Kaufmann, S.H.E. T cell clones and their products: Experimental clues for the immunoprophylaxis and immunotherapy of intracellular bacterial infections?. Infection 12, 124–129 (1984). https://doi.org/10.1007/BF01641694
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DOI: https://doi.org/10.1007/BF01641694