Interleukin-10 production by effector T cells: Th1 cells show self control

Abstract

Interleukin (IL)-10 is a cytokine that modulates both innate and adaptive immunity, primarily by exerting antiinflammatory effects. IL-10 was originally thought to be produced only by T helper (Th)2 cells, but is now known to be made by a variety of cell types. During many infections, CD4(+) T cells produce both interferon (IFN)-gamma, the signature Th1 cytokine, and IL-10. New data now show that the IL-10 produced by effector Th1 cells helps limit the collateral damage caused by exaggerated inflammation. But this control may also limit the effectiveness of the immune response, resulting in a failure to fully eliminate pathogens.

Figure 1.

T. gondii infection in C57BL/6 mice. (A) In intact animals, IFN-γ–producing Th1 cells efficiently control the infection. Some of these Th1 cells also produce IL-10, which helps limit the Th1 response and limit inflammation. (B) Blocking IFN-γ or IL-12 allows the infection to proceed unchecked, causing the rapid death of the animals. (C) Blocking the production of IL-10 by Th1 cells triggers an overproduction of proinflammatory cytokines by T cells and innate cells, resulting in the death of the infected animals, despite parasite clearance.

Figure 2.

L. major NIH/Sd infection in C57BL/6 mice. (A) In intact animals, IFN-γ–producing Th1 cells only partially control the infection, and nonhealing lesions are established. (B) Blocking the production of IL-10 by Foxp3⁻ Th1 cells increases the Th1 effector response, which helps clear the infection. (C) Depleting Foxp3⁺ T reg cells increases the parasite burden in parallel with the production of IL-10 and Th2 cytokines, resulting in increased susceptibility to infection.