A20 is an antigen presentation attenuator, and its inhibition overcomes regulatory T cell–mediated s

Abstract

Regulatory T cells (Treg cells) suppress autoreactive immune responses and limit the efficacy of tumor vaccines; however, it remains a challenge to selectively eliminate or inhibit Treg cells. In this study, the zinc-finger A20, a negative regulator of the Toll-like receptor and tumor necrosis factor receptor signaling pathways, was found to play a crucial part in controlling the maturation, cytokine production and immunostimulatory potency of dendritic cells (DCs). A20-silenced DCs showed spontaneous and enhanced expression of costimulatory molecules and proinflammatory cytokines and had different effects on T cell subsets: they inhibited Treg cells and hyperactivated tumor-infiltrating cytotoxic T lymphocytes and T helper cells that produced interleukin-6 and tumor necrosis factor-α and were refractory to Treg cell–mediated suppression. Hence, this study identifies A20 as an antigen presentation attenuator in control of antitumor immune responses during both the priming and the effector phases and provides a strategy to overcome Treg cell–mediated suppression in an antigen-specific manner, reducing the need to directly target Treg cells.

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Song, XT., Kabler, K., Shen, L. et al. A20 is an antigen presentation attenuator, and its inhibition overcomes regulatory T cell–mediated suppression. Nat Med 14, 258–265 (2008). https://doi.org/10.1038/nm1721

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