IL-10–producing and naturally occurring CD4+ Tregs: limiting collateral damage
Anne O’Garra, Pedro L. Vieira, Paulo Vieira, Anne E. Goldfeld
Anne O’Garra, Pedro L. Vieira, Paulo Vieira, Anne E. Goldfeld
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IL-10–producing and naturally occurring CD4+ Tregs: limiting collateral damage

Abstract

Effective immune responses against pathogens are sometimes accompanied by strong inflammatory reactions. To minimize damage to self, the activation of the immune system also triggers anti-inflammatory circuits. Both inflammatory and anti-inflammatory reactions are normal components of the same immune response, which coordinately fight infections while preventing immune pathology. IL-10 is an important suppressive cytokine, produced by a large number of immune cells in addition to the antigen-driven IL-10–producing regulatory and the naturally occurring suppressor CD4+ T cells, which is a key player in anti-inflammatory immune responses. However, additional mechanisms have evolved to ensure that pathogen eradication is achieved with minimum damage to the host. Here we discuss those mechanisms that operate to regulate effector immune responses.

Authors

Anne O’Garra, Pedro L. Vieira, Paulo Vieira, Anne E. Goldfeld

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Figure 1

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Layers of regulation of the immune response. At low levels of inflammati...
Layers of regulation of the immune response. At low levels of inflammation (A) both Foxp3+ naturally occurring Tregs and Foxp3– IL-10 Tregs inhibit CD4+ T cell proliferation through IL-10–independent, cell contact–dependent mechanisms. (B) Similar mechanisms may control immune responses to self antigens and autoimmune pathologies associated with low-level inflammation such as gastritis. (C) When strong inflammation occurs, with activation of APCs, effector molecules, such as IL-10 and TGF-β, secreted by Tregs are required to control CD4+ T cell responses. TLR, Toll-like receptor.