CD4+CD25−Foxp3− Th1 cells are the source of IL-10–mediated immune suppression in chronic cutaneous leishmaniasis

By Charles F. Anderson, M. Oukka, Vijay Kuchroo, D. Sacks. Journal of Experimental Medicine, 2007

640 citations recorded by the source corpus.

Nonhealing forms of leishmaniasis in humans are commonly associated with elevated levels of the deactivating cytokine IL-10, and in the mouse, normally chronic infections can be cleared in the absence of IL-10. Using a Leishmania major strain that produces nonhealing dermal lesions in a T helper type 1 (Th1) cell–polarized setting, we have analyzed the cellular sources of IL-10 and their relative contribution to immune suppression. IL-10 was produced by innate cells, as well as CD4+CD25+Foxp3+ and CD4+CD25−Foxp3− T cells in the chronic lesion. Nonetheless, only IL-10 production by antigen-specific CD4+CD25−Foxp3− T cells, the majority of which also produced IFN-γ, was necessary for suppression of acquired immunity in Rag−/− reconstituted mice. Surprisingly, Rag−/− mice reconstituted with naive CD4+ T cells depleted of natural T regulatory cells developed more severe infections, associated with elevated levels of IL-10 and, especially, Th2 cytokines in the site. The data demonstrate that IL-10–producing Th1 cells, activated early in a strong inflammatory setting as a mechanism of feedback control, are the principal mediators of T cell–derived IL-10–dependent immune suppression in a chronic intracellular infection.

Subfields: Immunology, Public Health, Environmental and Occupational Health, Rheumatology

View Paper: https://www.semanticscholar.org/paper/1f8865d3a55b4518fd6326c02a51ab0af3de108a

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Citations in the corpus

• Th17 cells in human disease (2008, background): “T-cell sources of IL-10 are generally thought to include Th2 cells and various types of Tregs, but Th1 cells have also been found to secrete IL-10 in certain conditions and to thereby limit their own inflammatory effects (50, 51).”
• Interleukin-10: new perspectives on an old cytokine (2008, background): “There is no question that Th1 cells and more recently Th17 cells are capable of producing IL-10, and these cells represent an important source of IL-10 during infectious diseases (13, 14), but it seems more likely that this production may occur as a homeostatic mechanism to prevent uncontrolled T-ce”