Conventional T-bet(+)Foxp3(-) Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection.

Abstract

Although interferon gamma (IFN-gamma) 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-gamma effector functions. We analyzed the source of regulatory IL-10 in mice infected with the protozoan parasite Toxoplasma gondii. Unexpectedly, IFN-gamma-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-gamma(gamma) 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-gamma, IL-10 production could be stimulated in IL-10(-)IFN-gamma(+) cells by further activation in vitro. In addition, experiments with T. gondii-specific IL-10(+)IFN-gamma(+) CD4 clones revealed that although IFN-gamma 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.

• Authors: Dragana Jankovic, Marika C Kullberg, Carl G Feng, Romina S Goldszmid, Carmen M Collazo, Mark Wilson, Thomas A Wynn, Masahito Kamanaka, Richard A Flavell, Alan Sher
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 204 Issue 2 Pg. 273-83 (Feb 19 2007) ISSN: 0022-1007 [Print] United States
• PMID: 17283209 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Antibodies, Monoclonal
• Cytokines
• Interleukin-10
• Interferon-gamma

Topics

• Animals
• Antibodies, Monoclonal (immunology)
• Cytokines (blood)
• Interferon-gamma (metabolism)
• Interleukin-10 (immunology, metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Signal Transduction (immunology)
• Th1 Cells (metabolism)
• Toxoplasma (immunology)
• Toxoplasmosis (immunology)