{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T10:06:35Z","timestamp":1791021995194,"version":"4.1.0"},"reference-count":28,"publisher":"American Society of Hematology","issue":"2","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,1,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic active Epstein-Barr virus (CAEBV) typically presents as persistent infectious mononucleosis-like disease and\/or hemophagocytic lymphohistocytosis (HLH), reflecting ectopic Epstein-Barr virus (EBV) infection and lymphoproliferation of T and\/or NK cells. Clinical behavior ranges from indolent, stable disease through to rapidly progressive, life-threatening disease. Although 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 vs coresident noninfected population, nor about the mechanisms that could underpin their evasion of host immune surveillance. To investigate these questions, we developed a multicolor flow cytometry technique combining phenotypic and functional marker staining with in situ hybridization for the EBV-encoded RNAs (EBERs) expressed in every infected cell. This allows the identification, phenotyping, and functional comparison of infected (EBERPOS) and noninfected (EBERNEG) lymphocyte subset(s) in patients\u2019 blood samples ex vivo. We have characterized 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\u2019 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 patient with CAEBV studied: the presence of large numbers of myeloid-derived suppressor cells that exhibited robust inhibition of T-cell growth. We suggest that their influence is likely to explain the host\u2019s failure to contain EBV-positive T\/NK-cell proliferation.<\/jats:p>","DOI":"10.1182\/blood.2020005611","type":"journal-article","created":{"date-parts":[[2020,8,25]],"date-time":"2020-08-25T17:54:55Z","timestamp":1598378095000},"page":"203-215","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":43,"title":["Characterizing EBV-associated lymphoproliferative diseases and the role of myeloid-derived suppressor cells"],"prefix":"10.1182","volume":"137","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2325-3265","authenticated-orcid":false,"given":"Paul J.","family":"Collins","sequence":"first","affiliation":[{"name":"1Institute for Immunology and Immunotherapy,"},{"name":"2Cancer Research UK Birmingham Centre, The University of Birmingham, Birmingham, United 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