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

Trinchieri G - J. Exp. Med. (2007)

Bottom Line: 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.But this control may also limit the effectiveness of the immune response, resulting in a failure to fully eliminate pathogens.

View Article: PubMed Central - PubMed

Affiliation: Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. trinchig@mail.nih.gov

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.

Show MeSH

Related in: MedlinePlus

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.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2118719&req=5

fig2: 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.

Mentions: Anderson et al. now characterize the source of IL-10 in C57BL/6 mice infected intradermally with a clinical isolate of L. major (NIH/Sd) that produces heavily infected, nonhealing lesions, even in the presence of a vigorous Th1 response (6). This experimental model is reminiscent of clinical leishmaniasis, which is characterized by a Th1-type response associated with IL-10 production that, in some cases, fails to induce healing or to prevent visceral spreading of the infection. In mice infected with L. major NIH/Sd, the IL-10 produced by T cells, but not by innate cells, was required for the suppression of the healing response, although most of the IL-10 at the lesion site was produced by innate cells (Fig. 2 A). The majority of IL-10 in the draining LNs, on the other hand, was produced by T cells, including both CD25+ Foxp3+ T reg cells and CD4+ CD25− Foxp3− T cells. A majority of the latter cells also produced IFN-γ (6).


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

Trinchieri G - J. Exp. Med. (2007)

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.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2118719&req=5

fig2: 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.
Mentions: Anderson et al. now characterize the source of IL-10 in C57BL/6 mice infected intradermally with a clinical isolate of L. major (NIH/Sd) that produces heavily infected, nonhealing lesions, even in the presence of a vigorous Th1 response (6). This experimental model is reminiscent of clinical leishmaniasis, which is characterized by a Th1-type response associated with IL-10 production that, in some cases, fails to induce healing or to prevent visceral spreading of the infection. In mice infected with L. major NIH/Sd, the IL-10 produced by T cells, but not by innate cells, was required for the suppression of the healing response, although most of the IL-10 at the lesion site was produced by innate cells (Fig. 2 A). The majority of IL-10 in the draining LNs, on the other hand, was produced by T cells, including both CD25+ Foxp3+ T reg cells and CD4+ CD25− Foxp3− T cells. A majority of the latter cells also produced IFN-γ (6).

Bottom Line: 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.But this control may also limit the effectiveness of the immune response, resulting in a failure to fully eliminate pathogens.

View Article: PubMed Central - PubMed

Affiliation: Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. trinchig@mail.nih.gov

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.

Show MeSH
Related in: MedlinePlus