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in IL-12-Deficient Mice During Toxoplasma gondii Infection1
Departments of
*
Physiology,
Microbiology, and
Medicine, Dartmouth Medical School, Lebanon, NH 03756
The importance of IFN-
in regulating the host CD8+ T
cell response during microbial infection has not been delineated. Mice
deficient for the p40 chain of the IL-12 heterodimer have impaired
IFN- production and are susceptible to infection with the
intracellular parasite Toxoplasma gondii. The
administration of exogenous IFN- to parasite-infected
p40-/- mice increases survival and up-regulates the
depressed CD8+ T cell response following infection.
CD8+ T cells isolated from cytokine-treated
p40-/- mice exhibit an increase in both precursor CTL
frequency and IFN- production compared with untreated controls. The
enhancement of the CD8+ T cell response is independent of
CD4+ T cell help. These CD8+ T cells induce
protective immunity against a lethal challenge when adoptively
transferred into naive p40-/- and
IFN--/- mice. These observations indicate that IFN-
can regulate the CD8+ T cell response during T.
gondii infection.
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