Abstract # I-25

Francisella tularensis strain LVS readily establishes a lethal infection in mice, and survival of sublethal infection generates very strong specific protective immunity. These studies characterize the immunological basis of that protection. Long term protection and clearance required both cytokine (TNF/IFN ) production and either CD4⁺ or CD8⁺ T cells, typical of intracellular bacteria. Unexpectedly, B cells as well as / ⁺ T cells were necessary for maximal long term protection. A novel early protective mechanism has also been found. Three days following sublethal intradermal LVS infection (priming), normal or nu/nu mice, but not immunodeficient scid mice, survived a lethal intraperitoneal (IP) challenge of 10⁵ LD₅₀s. Scid mice reconstituted intravenously with 2x10⁷ normal spleen cells, nu/nu spleen cells, or purified B cells and then primed and challenged with a 10⁴ lethal dose of LVS IP, survived. Reconstituted mice produced little specific antibody (Ab), however. B cell- mice, but not T cell- mice, died following priming and challenge. These results indicate a unique and very strong B cell dependent / Ab independent protection operative very early after infection; early protection also appears nonspecific. Thus study of the LVS model reveals common and unique mechanisms of protective immunity to intracellular bacteria that may be relevant to rational vaccine design.