Antigen-specific suppression of a primed immune response by dendritic cells mediated by regulatory T cells secreting interleukin-10

Immunity. 2003 Jan;18(1):155-67. doi: 10.1016/s1074-7613(02)00503-4.


Antigen-specific suppression of a previously primed immune response is a major challenge for immunotherapy of autoimmune disease. RelB activation is required for myeloid DC differentiation. Here, we show that antigen-exposed DCs in which RelB function is inhibited lack cell surface CD40, prevent priming of immunity, and suppress previously primed immune responses. DCs generated from CD40-deficient mice similarly confer suppression. Regulatory CD4+ T cells induced by the DCs transfer antigen-specific "infectious" tolerance to primed recipients in an interleukin-10-dependent fashion. Thus CD40, regulated by RelB activity, determines the consequences of antigen presentation by myeloid DCs. These observations have significance for autoimmune immunotherapy and suggest a mechanism by which peripheral tolerance might be constitutively maintained by RelB(-) CD40(-) DCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens
  • Autoimmune Diseases / therapy
  • CD4-Positive T-Lymphocytes / immunology*
  • CD40 Antigens / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Hemocyanins
  • Immune Tolerance
  • Immunotherapy
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / biosynthesis*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Ovalbumin / immunology
  • Proto-Oncogene Proteins / deficiency
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / immunology
  • Transcription Factor RelB
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / immunology


  • Antigens
  • CD40 Antigens
  • Proto-Oncogene Proteins
  • Relb protein, mouse
  • Transcription Factors
  • Interleukin-10
  • Transcription Factor RelB
  • Interferon-gamma
  • Ovalbumin
  • Hemocyanins
  • keyhole-limpet hemocyanin