Type 1 and type 2 cytokines in antiviral defense.
Ectromelia virus (EV) is a natural mouse pathogen that causes a generalized infection termed mousepox, which, in the genetically resistant C57BL/6 (B6) mouse, is an inapparent disease. In contrast, BALB/c and A strain mice are highly susceptible; one infectious virus particle can result in 100% mortality. The contribution of cytokines in the induction of protective immune responses and recovery from infection with EV in B6, BALB/c and A strain mice have been. In the spleen and lymph node (LN) of resistant B6 mice, IL-2, IFN-gamma and TNF-alpha were induced rapidly with large numbers of cells producing these cytokines. All three cytokines were virtually absent in BALB/c and A strain mice. No significant differences were found in the numbers of IL-4 producing cells in the spleen or LN of both resistant and susceptible mice. IFN-gamma-producing cells were detected in the spleen but not in the lymph node whereas IL-2-producing cells were detected only in the lymph node of B6 mice. Despite significant increases in the IFN-gamma mRNA levels in the LN of B6 mice, no protein was detected by immunocytochemistry. The mRNA levels of IL-2, TNF-alpha and IL-12 were also rapidly upregulated in LN of B6 mice. The rapid induction of type I cytokines strongly correlated with a potent antiviral CTL response in B6 mice. The absence of these cytokines also correlated with a complete absence or delayed induction of CTL responses to EV in both the BALB/c and A strain mice. IFN-gamma gene knock out mice on a B6 background were as susceptible to EV as the BALB/c and A strain mice.
Karupiah
G
G
Division of Immunology and Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra ACT, Australia. guna.karupiah@anu.edu.au
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004481:Ectromelia virus / Q000276:immunology* / Q000472:pathogenicity*; D004482:Ectromelia, Infectious / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000914:Antibodies, Viral; D016207:Cytokines