CD40L stimulation of rat dendritic cells specifically favors the IL-12/IL-10 ratio resulting in a strong T cell stimulatory capacity

Mol Immunol. 2008 May;45(9):2641-50. doi: 10.1016/j.molimm.2007.12.014. Epub 2008 Feb 8.

Abstract

Dendritic cells (DC) play an important role in immune responses and have been studied extensively in human and mouse models. CD40 triggering of DC has a pivotal role in their maturation process, obtaining the unique capacity to induce strong CD4 and CD8 T cell activation. Although rat models are frequently used for the understanding of the underlying mechanism of human diseases, relatively little is known about rat DC. To investigate the effect of CD40 triggering on rat DC, we cloned the rat CD40L gene and generated murine fibroblasts with stable expression (L-rCD40L). DC stimulated by L-rCD40L cells exhibited a strong T cell stimulatory capacity, associated with higher amounts of IFN-gamma as compared to LPS-stimulated DC. Analysis of cytokine production showed that LPS induced both IL-12 and IL-10 production, whereas CD40L induced high amounts of IL-12, but little IL-10 production by rat DC. This implies that the difference found in T cell stimulatory capacity by the stimulated DC is due to the cytokine profile of the DC at the time of T cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD40 Ligand / immunology*
  • CD40 Ligand / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Humans
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism*
  • Interleukin-12 / immunology
  • Interleukin-12 / metabolism*
  • Lipopolysaccharides / immunology
  • Lymphocyte Activation*
  • Male
  • Mice
  • Mice, Transgenic
  • Rats
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Lipopolysaccharides
  • Interleukin-10
  • CD40 Ligand
  • Interleukin-12
  • Interferon-gamma