Cytotoxic T lymphocyte antigen-4-dependent down-modulation of costimulatory molecules on dendritic cells in CD4+ CD25+ regulatory T-cell-mediated suppression

Immunology. 2006 Jun;118(2):240-9. doi: 10.1111/j.1365-2567.2006.02362.x.

Abstract

We have previously demonstrated that CD4+ CD25+ natural regulatory T cells (Treg cells) induce down-modulation of CD80 and CD86 (B7) molecules on dendritic cells (DCs) in vitro. In this report we show that the extent of down-modulation is functionally significant because Treg-cell conditioned DCs induced poor T-cell proliferation responses. Further, we report that down-modulation was induced rapidly and was inhibited by blocking cytotoxic T lymphocyte antigen-4 (CTLA-4), which is constitutively expressed by the Treg cells. Even though Treg cells have previously been reported to kill antigen-presenting cells, the down-modulation was not due to selective killing of DCs expressing high level of the costimulatory molecules. We propose that Treg cells down-modulate B7-molecules on DCs in a CTLA-4-dependent way, thereby enhancing suppression of T-cell activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Antigens, CD
  • Antigens, Differentiation / immunology*
  • B7-1 Antigen / metabolism
  • B7-2 Antigen / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • CTLA-4 Antigen
  • Cell Survival / immunology
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Down-Regulation / immunology
  • Female
  • Immune Tolerance*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Receptors, Interleukin-2 / analysis
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • B7-1 Antigen
  • B7-2 Antigen
  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • Receptors, Interleukin-2