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¹ Immunobiology Section and ² Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892
³ Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520

CORRESPONDENCE Dragana Jankovic: DJankovic{at}niaid.nih.gov

Although interferon (IFN-) secretion is essential for control of most intracellular pathogens, host survival often also depends on the expression of interleukin 10 (IL-10), a cytokine known to counteract IFN- effector functions. We analyzed the source of regulatory IL-10 in mice infected with the protozoan parasite Toxoplasma gondii. Unexpectedly, IFN-–secreting T-bet⁺Foxp3^– T helper type 1 (Th1) cells were found to be the major producers of IL-10 in these animals. Further analysis revealed that the same IL-10⁺IFN- population displayed potent effector function against the parasite while, paradoxically, also inducing profound suppression of IL-12 production by antigen-presenting cells. Although at any given time point only a fraction of the cells appeared to simultaneously produce IL-10 and IFN-, IL-10 production could be stimulated in IL-10^–IFN-⁺ cells by further activation in vitro. In addition, experiments with T. gondii–specific IL-10⁺IFN-⁺ CD4 clones revealed that although IFN- expression is imprinted and triggered with similar kinetics regardless of the state of Th1 cell activation, IL-10 secretion is induced more rapidly from recently activated than from resting cells. These findings indicate that IL-10 production by CD4⁺ T lymphocytes need not involve a distinct regulatory Th cell subset but can be generated in Th1 cells as part of the effector response to intracellular pathogens.

M.C. Kullberg's present address is Immunology and Infection Unit, Dept. of Biology, University of York and Hull York Medical School, York YO10 5YW, England, UK.

C.M. Collazo's present address is Division of Vaccines and Related Products Applications, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852.

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