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

Authors

  • U.E. Hoepken
  • I. Lehmann
  • J. Droese
  • M. Lipp
  • T. Schueler
  • A. Rehm

Journal

  • European Journal of Immunology

Citation

  • Eur J Immunol 35 (10): 2851-2863

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 NKI.I 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.


DOI

doi:10.1002/eji.200526298