The ratio between dendritic cells and T cells determines the outcome of their encounter: proliferation versus deletion

Eur J Immunol. 2005 Oct;35(10):2851-63. doi: 10.1002/eji.200526298.

Abstract

Dendritic cells (DC) either induce T cell tolerance or contribute to the initiation and modulation of T and B cell responses. Since many of the variables determining the thresholds of naive T cell priming were defined in vitro using a homogeneously matured DC population, we here focused on partially mature DC which might reflect the occurrence of tumor-infiltrating and thymic DC. To predict how those DC regulate the induction of antigen-specific T cell proliferation and T cell tolerance, we co-cultured ovalbumin-pulsed murine DC at different ratios with antigen-specific DO11.10 transgenic T cells. Whereas partially mature DC at a DC/T cell ratio of 1:10 supported proliferation, a DC/T cell ratio of 1:2 induced proliferation arrest in naive CD4+ T cells. The acquisition of the NK cell inhibitory markers NK1.1 and KLRG on T cells exposed to high numbers of DC suggests a role for these molecules in the protection of antigen-responsive T cells from exhaustion by overstimulation. Mechanistically, abortive T cell proliferation upon encounter of high numbers of partially mature DC is caused by an apoptosis-related pathway, suggesting that excessive antigen density without sufficient costimulation results in activation-induced cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Apoptosis / immunology
  • Cell Communication / immunology
  • Cell Line, Tumor
  • Cell Proliferation
  • Coculture Techniques
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Female
  • Flow Cytometry
  • Immune Tolerance*
  • Lectins, C-Type
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Immunologic / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*

Substances

  • Klrg1 protein, mouse
  • Lectins, C-Type
  • Receptors, Antigen, T-Cell
  • Receptors, Immunologic