Inherited CD70 deficiency in humans reveals a critical role for the CD70-CD27 pathway in immunity to Epstein-Barr virus infection

J Exp Med. 2017 Jan;214(1):73-89. doi: 10.1084/jem.20160784. Epub 2016 Dec 23.


Epstein-Barr virus (EBV) infection in humans is a major trigger of malignant and nonmalignant B cell proliferations. CD27 is a co-stimulatory molecule of T cells, and inherited CD27 deficiency is characterized by high susceptibility to EBV infection, though the underlying pathological mechanisms have not yet been identified. In this study, we report a patient suffering from recurrent EBV-induced B cell proliferations including Hodgkin's lymphoma because of a deficiency in CD70, the ligand of CD27. We show that EBV-specific T lymphocytes did not expand properly when stimulated with CD70-deficient EBV-infected B cells, whereas expression of CD70 in B cells restored expansion, indicating that CD70 on B cells but not on T cells is required for efficient proliferation of T cells. CD70 was found to be up-regulated on B cells when activated and during EBV infection. The proliferation of T cells triggered by CD70-expressing B cells was dependent on CD27 and CD3 on T cells. Importantly, CD27-deficient T cells failed to proliferate when stimulated with CD70-expressing B cells. Thus, the CD70-CD27 pathway appears to be a crucial component of EBV-specific T cell immunity and more generally for the immune surveillance of B cells and may be a target for immunotherapy of B cell malignancies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / immunology
  • CD27 Ligand / deficiency
  • CD27 Ligand / genetics
  • CD27 Ligand / physiology*
  • Child
  • Codon, Nonsense
  • Epstein-Barr Virus Infections / immunology*
  • Humans
  • Lymphocyte Activation
  • Male
  • Receptors, Antigen, T-Cell / physiology
  • Signal Transduction / physiology*
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / physiology*


  • CD27 Ligand
  • CD70 protein, human
  • Codon, Nonsense
  • Receptors, Antigen, T-Cell
  • Tumor Necrosis Factor Receptor Superfamily, Member 7

Associated data

  • PDB/1DG6
  • PDB/1D0G