Characterising EBV-associated lymphoproliferative diseases and the role of myeloid-derived suppressor cells

Paul Collins, Christopher P. Fox, Lindsay C. George, Hayden Pearce, Gordon Brendan Ryan, Carmela De Santo, Francis Jay Mussai, David Lewis, Heather M. Long, Claire D. Shannon-Lowe

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Chronic active Epstein Barr virus (CAEBV) typically presents as persistent infectious mononucleosis-like disease and/or haemophagocytic lymphohistocytosis, reflecting ectopic EBV infection and lymphoproliferation of T and/or NK-cells. Clinical behaviour ranges from indolent, stable disease through to rapidly progressive, life-threatening disease. Whilst it is thought the chronicity and/or progression reflect an escape from immune control, very little is known about the phenotype and function of the infected cells versus co-resident non-infected population, nor about the mechanisms that could underpin their evasion of host immune surveillance. To investigate these questions, we developed a multicolour flow cytometry technique combining phenotypic and functional marker staining with in-situ hybridisation for the EBER RNAs expressed in every infected cell. This allows the identification, phenotyping and functional comparison of infected (EBERPOS) and non-infected (EBERNEG) lymphocyte subset(s) in patients' blood samples ex vivo. We have characterised CAEBV and HLH cases with monoclonal populations of discrete EBV-activated T-cell subsets, in some cases accompanied by EBV-activated NK-cell subsets, with longitudinal data on the infected cells' progression despite standard steroid-based therapy. Given that cytotoxic CD8+ T-cells with relevant EBV antigen specificity were detectable in the blood of the best studied patient, we searched for means whereby host surveillance might be impaired. This revealed a unique feature in almost every CAEBV patient studied: the presence of large numbers of myeloid derived suppressor cells which exhibited robust inhibition of T-cell growth. We suggest that their influence is likely to explain the host's failure to contain EBV-positive T/NK-cell proliferation.

Original languageEnglish
Pages (from-to)203–215
Number of pages13
Issue number2
Early online date25 Aug 2020
Publication statusPublished - 14 Jan 2021


  • Epstein-Barr Virus Infections
  • Herpesvirus 4, Human
  • Lymphoproliferative Disorders
  • Myeloid-Derived Suppressor Cells
  • antigens
  • crossbreeding
  • flow cytometry
  • indolent
  • infectious mononucleosis
  • phenotype determination


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