Expression of costimulatory ligand CD70 on steady-state dendritic cells breaks CD8+ T cell tolerance and permits effective immunity

Immunity. 2008 Dec 19;29(6):934-46. doi: 10.1016/j.immuni.2008.10.009. Epub 2008 Dec 8.


Steady-state dendritic cells (DCs) maintain peripheral T cell tolerance, whereas mature DCs generate immunity. CD70 is a costimulatory ligand acquired upon DC maturation. To determine its impact on T cell fate, we have generated mice that constitutively express CD70 in conventional DCs (cDCs). In these mice, naive CD4+ and CD8+ T cells spontaneously convert into effector cells. Administration of peptide without adjuvant, which is ordinarily tolerogenic, elicited tumor-eradicating CD8+ T cell responses and robust CD4+ T cell-independent memory. CD70 was also constitutively expressed in cDCs that inducibly present viral epitopes. In this case, tolerance induction was prevented as well. The antigen-presenting DCs generated protective immunity to virus infection and broke a pre-existing state of CD8+ T cell tolerance. Thus, the sole expression of CD70 by otherwise immature cDCs sufficed to convert CD8+ T cell tolerance into immunity, defining the importance of CD27-CD70 interactions at the interface between T cell and DC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD27 Ligand / genetics
  • CD27 Ligand / immunology*
  • CD27 Ligand / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Immune Tolerance / immunology*
  • Immunologic Memory
  • Melanoma / immunology
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Neoplasms / immunology*
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism


  • CD27 Ligand
  • OVA-8
  • Peptide Fragments
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Ovalbumin