Tularaemia in the rat. I. The cellular basis on host resistance to infection.

Rats infected with the live vaccine strain (LVS) of Francisella tularensis develop in vivo and in vitro evidence of cellular hypersensitivity and a concomitant state of cellular resistance to infection. They key role of sensitized lymphocytes in cellular resistance was domonstrated in transfer experiments. Using this technique, it was shown that thoracic duct lymphocytes from Francisella immune donors conferred specific antimicrobial resistance on normal recipients, whereas antiserum afforded no protection whatsoever. Further evidence for the participation of sensitized lymphocytes in the host's defence emerged from experiments in which a comparative analysis was made of the immunogenic properties of living and heat-killed LVS organisms. Rats stimulated with the living parasite developed cellular hypersensitivity and specific antibodies. Throacic duct lymphocytes obtained from such animals could immunize adoptively. By comparison, rats stimulated with a substantially larger number of dead organisms failed to develop cellular hypersensitivity and their lymphocytes were devoid of protective activity. Dead organisms, however, provoked an antibody response similar to that observed in infected rats. The development of cellular hypersensitivity in Francisella-infected rats is associated with enhanced resistance to Listeria monocytogenes. This finding accords with the results of similar studies of infection immunity to other intracellular parasites, and implies that the expression of cellular resistance to F. tularensis is a cooperative venture involving specifically sensitized lymphocytes and non-specific inflammatory cells, presumably macrophages.