T-cell-independent resistance to infection and generation of immunity to Francisella tularensis.
The intraperitoneal 50% lethal dose (LD50) for Francisella tularensis LVS in both normal control heterozygote BALB/c nu/+ mice and BALB/c nu/nu mice was 2 x 10(0). Both nu/+ and nu/nu mice given 10(7) LVS bacteria or more intradermally (i.d.) died, with a mean time to death of about 7 to 8 days. On the other hand, nu/+ mice given 10(6) LVS bacteria or less survived for more than 60 days and cleared systemic bacteria, while nu/nu mice given 10(6) LVS bacteria or less survived for more than 10 days but died between days 25 and 30. Thus, the short-term (i.e., < 10-day) i.d. LD50 of both nu/nu and nu/+ mice was 3 x 10(6), but the long-term (i.e., > 10-day) i.d. LD50 of nu/nu mice was less than 7 x 10(0). The short-term survival of i.d. infection was dependent on tumor necrosis factor and gamma interferon: treatment of nu/nu mice with anti-tumor necrosis factor or anti-gamma interferon at the time of i.d. infection resulted in death from infection 7 to 8 days later, whereas control infected nu/nu mice survived for 26 days. nu/nu mice infected with LVS i.d. generated LVS-specific serum antibodies, which were predominantly immunoglobulin M: titers peaked 7 days after i.d. infection but declined sharply by day 21, after which mice died. Surprisingly, nu/nu mice given 10(3) LVS bacteria i.d. became resistant to a lethal challenge (5,000 LD50s) of LVS intraperitoneally within 2 days after i.d. infection; nu/nu mice similarly infected with LVS i.d. and challenged with Salmonella typhimurium (10 LD50s) were not protected. nu/nu mice given nu/+ spleen cells intravenously as a source of mature T cells survived i.d. infection for more than 60 days and cleared bacteria. Taken together, these studies demonstrate that i.d. infection of nu/nu mice with LVS rapidly generates T-cell-independent, short-term, specific protective immunity against lethal challenge, but T lymphocytes are essential for long-term survival.
Elkins
K L
KL
Department of Cellular Immunology, Walter Reed Army Institute of Research, Rockville, Maryland 20850.
Rhinehart-Jones
T
T
Nacy
C A
CA
Winegar
R K
RK
Fortier
A H
AH
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D005604:Francisella tularensis / Q000276:immunology*; D007109:Immunity; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000502:physiology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014406:Tularemia / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000907:Antibodies, Bacterial; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma