IL-6 produced by type I IFN DC controls IFN-gamma production by regulating the suppressive effect of CD4+ CD25+ regulatory T cells

Hum Immunol. 2005 May;66(5):460-8. doi: 10.1016/j.humimm.2005.01.012. Epub 2005 Feb 26.

Abstract

The dendritic cell family is composed of different subsets differentially governing the immune response. Type I interferon (IFN) dendritic cells (DC) are endowed with the ability to trigger both Th1 and Th2 type responses. In view of the pivotal role of regulatory T cells in limiting the effectiveness of effector cells, we analyzed the interactions between these cells and type I IFN DC. DC were generated from monocytes in the presence of IFN-beta and interleukin (IL)-3 (DCI3) or granulocyte macrophage-colony-stimulating factor and IL-4 (DCG4) and activated by poly(I:C). Despite the release of lower amounts of IL-12 after maturation, DCI3 were able to induce a higher IFN-gamma production by T lymphocytes during the mixed leucocyte reaction (MLR) as compared with DCG4. mRNA analysis disclosed that DCI3 overtranscribed the IL-6 gene and secreted high amounts of the protein. Neutralization of IL-6 revealed that this cytokine specifically contributed to the IFN-gamma release induced by DCI3. Finally, depletion of CD25+ T cells before the MLR identified these cells as a target for IL-6. We conclude that DCI3 are endowed with the property of regulating the suppressive effect of regulatory T cells through high IL-6 production. This novel mechanism of T cell control is relevant for the use of DCI3 in vaccination strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / pharmacology
  • Antigens, CD / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Coculture Techniques
  • Cytokines / genetics
  • Cytokines / pharmacology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Gene Expression / drug effects
  • Gene Expression / immunology
  • Gene Expression Profiling
  • Humans
  • Interferon Type I / immunology
  • Interferon-alpha / genetics
  • Interferon-alpha / immunology
  • Interferon-alpha / metabolism
  • Interferon-gamma / metabolism*
  • Interleukin-12 / metabolism
  • Interleukin-12 Subunit p40
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology*
  • Interleukin-6 / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Lymphocyte Culture Test, Mixed
  • Poly I-C / pharmacology
  • Protein Subunits / metabolism
  • Receptors, Interleukin-2 / immunology*
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Antibodies
  • Antigens, CD
  • Cytokines
  • Interferon Type I
  • Interferon-alpha
  • Interleukin-12 Subunit p40
  • Interleukin-6
  • Protein Subunits
  • Receptors, Interleukin-2
  • Interleukin-12
  • Interferon-gamma
  • Poly I-C