Conventional T-bet+Foxp3− Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection
By Dragana Jankovic, M. Kullberg, C. Feng, R. Goldszmid, C. Collazo, M. Wilson, TA Wynn, M. Kamanaka, R. Flavell, A. Sher. Journal of Experimental Medicine, 2007
673 citations recorded by the source corpus.
Although interferon γ (IFN-γ) 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-γ effector functions. We analyzed the source of regulatory IL-10 in mice infected with the protozoan parasite Toxoplasma gondii. Unexpectedly, IFN-γ–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-γγ 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-γ, IL-10 production could be stimulated in IL-10−IFN-γ+ cells by further activation in vitro. In addition, experiments with T. gondii–specific IL-10+IFN-γ+ CD4 clones revealed that although IFN-γ 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.
Subfields: Epidemiology, Immunology, Parasitology
View Paper: https://www.semanticscholar.org/paper/f0e370e6d4de41acc922034d5db8d08b66c358e8
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In Epidemiology
In Immunology
- TA Wynn
- Xia Zhang
- Y. Belkaid
- M. Wilson
- D. Mosser
- Eleanor M. Riley
- Christopher A. Hunter
- Kevin N. Couper
In Parasitology
Citations in the corpus
- Decrease of Foxp3+ Treg cell number and acquisition of effector cell phenotype during lethal infection (2009, background): “gondii after intraperitoneal infection, IL-27, as well as IL-10-producing Th1 cells, limits excessive effector responses (Gazzinelli et al., 1996; Jankovic et al., 2007; Villarino et al., 2003).”
- Bleomycin and IL-1β–mediated pulmonary fibrosis is IL-17A dependent (2010, result): “, 2007) and similar to IFN and IL10 coexpressing cells (Anderson et al., 2007; Jankovic et al., 2007; Saraiva et al., 2009).”
- IL-10: The Master Regulator of Immunity to Infection (2008, background): “gondii, malaria, and leishmaniasis (17, 37, 64, 68).”