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