A role for interleukin-2 trans-presentation in dendritic cell-mediated T cell activation in humans, as revealed by daclizumab therapy

Nat Med. 2011 May;17(5):604-9. doi: 10.1038/nm.2365. Epub 2011 May 1.


Although previous studies have described CD25 expression and production of interleukin-2 (IL-2) by mature dendritic cells (mDCs), it remains unclear how these molecules participate in the activation of T cells. In search of the mechanisms by which daclizumab, a humanized monoclonal antibody against CD25, inhibits brain inflammation in multiple sclerosis, we observed that although the drug has limited effects on polyclonal T cell activation, it potently inhibits activation of antigen-specific T cells by mDCs. We show that mDCs (and antigen-experienced T cells) secrete IL-2 toward the mDC-T cell interface in an antigen-specific manner, and mDCs 'lend' their CD25 to primed T cells in trans to facilitate early high-affinity IL-2 signaling, which is crucial for subsequent T cell expansion and development of antigen-specific effectors. Our data reveal a previously unknown mechanism for the IL-2 receptor system in DC-mediated activation of T cells.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Antigen Presentation* / drug effects
  • Daclizumab
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Humans
  • Immunoglobulin G / pharmacology*
  • Immunosuppressive Agents / pharmacology
  • In Vitro Techniques
  • Interleukin-2 / immunology*
  • Interleukin-2 Receptor alpha Subunit / antagonists & inhibitors
  • Interleukin-2 Receptor beta Subunit / immunology
  • Lymphocyte Activation / drug effects
  • Models, Immunological
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / immunology
  • Signal Transduction
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Transplantation Tolerance / drug effects
  • Transplantation Tolerance / immunology


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • IL2 protein, human
  • IL2RA protein, human
  • IL2RB protein, human
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-2 Receptor beta Subunit
  • Daclizumab