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

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.
Kazushi Izawa 1,  Emmanuel Martin 1,  Claire Soudais 1 2,  Julie Bruneau 2 3,  David Boutboul 1,  Rémy Rodriguez 1 2,  Christelle Lenoir 1,  Andrew D Hislop 4,  Caroline Besson 5,  Fabien Touzot 2 6,  Capucine Picard 7 2 8 9,  Isabelle Callebaut 10,  Jean-Pierre de Villartay 11 2,  Despina Moshous 11 2 9,  Alain Fischer 2 9 12 13,  Sylvain Latour 14 2
Affiliations

Affiliations

  • 1 Laboratory of Lymphocyte Activation and Susceptibility to EBV infection, Institut National de la Santé et de la Recherche Médicale UMR 1163, 75015 Paris, France.
  • 2 University Paris Descartes Sorbonne Paris Cité, Imagine Institut, 75015 Paris, France.
  • 3 Department of Pathology, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France.
  • 4 School of Cancer Sciences, University of Birmingham, Birmingham B15 2TT, England, UK.
  • 5 Department of Biological Hematology and Immunology, Bicêtre Hospital, Assistance Publique-Hôpitaux de Paris, 94270 Le Kremlin-Bicêtre, France.
  • 6 Department of Biotherapy, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France.
  • 7 Laboratory of Human Genetics of Infectious Diseases, Institut National de la Santé et de la Recherche Médicale UMR 1163, 75015 Paris, France.
  • 8 Centre d'Etude des Déficits Immunitaires, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France.
  • 9 Department of Pediatric Immunology, Hematology, and Rheumatology, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France.
  • 10 Centre National de la Recherche Scientifique UMR 7590, Sorbonne Universities, University Pierre et Marie Curie-Paris 6-MNHN-IRD-IUC, 75005 Paris, France.
  • 11 Laboratory of Dynamic of Genome and Immune System, Institut National de la Santé et de la Recherche Médicale UMR 1163, 75015 Paris, France.
  • 12 Collège de France, 75005 Paris, France.
  • 13 Institut National de la Santé et de la Recherche Médicale UMR 1163, 75015 Paris, France.
  • 14 Laboratory of Lymphocyte Activation and Susceptibility to EBV infection, Institut National de la Santé et de la Recherche Médicale UMR 1163, 75015 Paris, France sylvain.latour@inserm.fr.
PMID: 28011863 DOI: 10.1084/jem.20160784
Abstract

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.

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