A20 is an antigen presentation attenuator, and its inhibition overcomes regulatory T cell-mediated suppression

Nat Med. 2008 Mar;14(3):258-65. doi: 10.1038/nm1721. Epub 2008 Mar 2.


Regulatory T cells (T(reg) cells) suppress autoreactive immune responses and limit the efficacy of tumor vaccines; however, it remains a challenge to selectively eliminate or inhibit T(reg) 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 T(reg) cells and hyperactivated tumor-infiltrating cytotoxic T lymphocytes and T helper cells that produced interleukin-6 and tumor necrosis factor-alpha and were refractory to T(reg) 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 T(reg) cell-mediated suppression in an antigen-specific manner, reducing the need to directly target T(reg) cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation*
  • Cell Differentiation
  • Cell Line
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism*
  • Cytokines / metabolism
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Gene Silencing
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Mice
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Neoplasms / immunology
  • RNA, Small Interfering
  • T-Lymphocytes, Regulatory / immunology*
  • Tumor Necrosis Factor alpha-Induced Protein 3


  • Cytokines
  • Intracellular Signaling Peptides and Proteins
  • RNA, Small Interfering
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Cysteine Endopeptidases
  • Tnfaip3 protein, mouse