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CUTTING EDGE |
Production in T Cells Mediating Chronic Resistance to the Intracellular Pathogen, Toxoplasma gondii
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
IL-12 is required for the development of IFN-
-dependent
resistance to intracellular pathogens but is not thought to play a
major role in its maintenance. To directly assess the requirement for
continuous IL-12 signaling in long-term cell-mediated immunity,
recombinant cytokine was transiently administered to IL-12
p40-deficient mice during the first 2 wk of infection with the
intracellular pathogen Toxoplasma gondii. As expected,
these animals survived the acute phase and established chronic
infections. However, 4–6 wk after IL-12 withdrawal, the mice exhibited
increased brain cyst burdens and succumbed to toxoplasmic encephalitis.
Reactivation was associated with a loss of T-dependent IFN-
production without a concomitant increase in Th2 cytokine expression.
Importantly, parasite Ag-induced IFN- synthesis by purified T cells
from these animals could be restored by in vitro exposure to IL-12.
These results argue that endogenous IL-12 is required for the long-term
maintenance of IFN--dependent resistance against intracellular
pathogens.
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