Experimental murine tularemia caused by Francisella tularensis, live vaccine strain: a model of acquired cellular resistance

We have established a model of experimentally-induced tularemia in mice, using the live vaccine strain of Francisella tularensis. A sublethal, intravenous inoculation of this organism caused in C57BL/6 strain mice an acute infection which lasted approximately 12 days. The clearance of Francisella from the bloodstream was shown to be complete by 5.5 hours post-infection. At this time, approximately twice as many bacteria were isolated from the Spleen as from the liver. Mice which had recovered from a primary infection demonstrated a significant resistance to re-infection with autologous Francisella, a memory which persisted for at least 15 weeks. Resistance to experimental tularemia could be passively transferred from infected mice to naive mice by means of non-adherent spleen cells. Cells capable of adoptive transfer of resistance were present at a maximal concentration 7 days following infection, and persisted in significant numbers within the spleen cell population for at least 20 days after infection. Treatment of mice with serum from recovered animals caused a decrease in resistance when measured in the livers, and an increase in resistance when measured in the spleens. Suppression of T cell-mediated immunity during infection by treatment with cyclosporin A resulted in a dramatic increase in the tissue bacterial counts. Cyclosporin A-induced suppression of anti-tularemic resistance was first noted 2–3 days following infection and remained apparent for at least 8 days. The results of these experiments demonstrate that resistance to experimental murine tularemia is mediated predominantly by a cell-mediated mechanism. This mechanism involves T cells which become activated as early as 2–3 days following infection. Experimental, non-lethal infection with Francisella tularensis is thus an excellent model for investigating the mechanisms of acquired cellular immunity.