Comparison of T cell cytokines in resistant and susceptible mice infected with virulent Brucella abortus strain 2308.
C57BL/10 and BALB/c mice differ in their abilities to clear infections with the intracellular bacterium Brucella abortus strain 2308. We have previously reported that in vivo of IL-10 in the susceptible BALB/c mice results in significantly fewer bacteria in their spleens 1 week after infection with 5 x 10(3) colony forming units (CFU) of 2308. Here we extend those studies and report a similar effect when IL-4 is neutralized. In contrast, in the more resistant C57BL/10 mice infected with 5 x 10(3) CFU, neither neutralization of IL-4 significantly decreased the level of infection nor did it in either BALB/c or C57BL/10 mice infected with a 1000-fold higher dose of strain 2308. While splenocytes from the later mentioned groups of mice produced IL-10 in response to stimulation with brucella antigen, they also produced higher levels of interferon (IFN)-gamma than those from BALB/c mice with the low challenge dose of 5 x 10(3) CFU. Results of in vivo neutralization of IFN-gamma by monoclonal antibodies (MAb) reported here and elsewhere indicated that IFN-gamma is important for control; thus, we postulate that the higher levels of IFN-gamma override the detrimental effects of Th2 cytokines. In vitro studies also showed that macrophages from the more resistant C57BL/10 mice were less susceptible to the ability of IL-10 to decrease anti-brucella activities than were BALB/c macrophages. CD4+ T cells were principally responsible for the production of IL-10 in BALB/c but not C57BL/10 splenocyte populations. C57BL/10 splenocytes produced more IFN-gamma than those from BALB/c mice in response to stimulation with brucella antigens. These differences between BALB/c and C57BL/10 mice may contribute to the superior capacity of C57BL/10 mice to control infections with B. abortus strain 2308.
Fernandes
D M
DM
Department of Veterinary and Animal Sciences, Paige Laboratory, University of Massachusetts, Amherst 01003, USA.
Jiang
X
X
Jung
J H
JH
Baldwin
C L
CL
D000818:Animals; D002003:Brucella abortus / Q000276:immunology*; D002006:Brucellosis / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D004198:Disease Susceptibility; D005260:Female; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000494:pharmacology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D016207:Cytokines; D016753:Interleukin-10; D007371:Interferon-gamma