Interleukin-4 acts at the locus of the antigen-presenting dendritic cell to counter-regulate cytotoxic CD8+ T-cell responses

Nat Med. 2001 Feb;7(2):206-14. doi: 10.1038/84659.


The mechanism underlying suppression of immune responses by interleukin-4 (IL-4) has remained unexplained. Here we show that the antigen-presenting dendritic cell is central to counter-regulation of autoimmune disease by IL-4. IL-4 acts at the locus of the dendritic cell to decrease the cytolytic T-cell response, preventing autoimmunity. Stimulation of cytotoxic precursors by antigen pulsed dendritic cells induces their differentiation but the process is blocked by IL-4. IL-4-influenced DC produce distinct effects on CD8+ T cells depending on their state of activation. The molecular basis for this regulation is the alteration of the expression ratio of the costimulatory ligands B7.1/B7.2 on dendritic cells. Our findings demonstrate that B7.2 induces expansion of CD8+ T cells and B7.1 governs their acquisition of cytolytic activity. IL-4 influences the dendritic cell to elicit qualitative differences in T-cell responses, providing the basis for counter-regulation mediated by IL-4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / biosynthesis
  • B7-1 Antigen / biosynthesis
  • B7-2 Antigen
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Survival
  • Cytosol / immunology
  • Dendritic Cells / immunology*
  • Diabetes Mellitus, Type 1 / immunology*
  • Humans
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology*
  • Islets of Langerhans / immunology
  • Islets of Langerhans / metabolism
  • Membrane Glycoproteins / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Nucleoproteins / immunology
  • Peptide Fragments / immunology
  • Peptides / immunology


  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • CD86 protein, human
  • Cd86 protein, mouse
  • Membrane Glycoproteins
  • Nucleoproteins
  • Peptide Fragments
  • Peptides
  • nucleoprotein peptide 118-126, lymphocytic choriomeningitis virus
  • Interleukin-4