{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:56:45Z","timestamp":1788271005544,"version":"build-2803163510"},"reference-count":0,"publisher":"American Society of Hematology","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Immune thrombocytopenia (ITP) is traditionally considered an antibody-mediated disease. However, a number of features suggest alternative mechanisms of platelet destruction. In this study, we use a multi-dimensional approach to explore the role of cytotoxic CD8+ T cells in ITP. We characterised patients with ITP and compared them to age-matched controls using immunophenotyping, next-generation sequencing of T cell receptor (TCR) genes, single-cell RNA sequencing, and functional T cell and platelet assays. We found that adults with chronic ITP have increased polyfunctional, terminally differentiated effector memory CD8+ T cells (CD45RA+CD62L-) expressing intracellular interferon-g, tumour necrosis factor-a, and Granzyme B defining them as TEMRA cells. These TEMRA cells expand when the platelet count falls and show no evidence of physiological exhaustion. Deep sequencing of the T cell receptor showed expanded T cell clones in patients with ITP. T cell clones persisted over many years, were more prominent in patients with refractory disease, and expanded when the platelet count was low. Combined single-cell RNA and TCR sequencing of CD8+ T cells confirmed that the expanded clones are TEMRA cells. Using in vitro model systems, we show that CD8+ T cells from patients with ITP form aggregates with autologous platelets, release interferon-g and trigger platelet activation and apoptosis through TCR-mediated release of cytotoxic granules. These findings of clonally expanded CD8+ T cells causing platelet activation and apoptosis provide an antibody-independent mechanism of platelet destruction, indicating that targeting specific T-cell clones could be a novel therapeutic approach for patients with refractory ITP.<\/jats:p>","DOI":"10.1182\/blood.2022018380","type":"journal-article","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T21:07:56Z","timestamp":1675804076000},"update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":25,"title":["The role of CD8+ T cell clones in immune thrombocytopenia"],"prefix":"10.1182","author":[{"given":"Amna","family":"Malik","sequence":"first","affiliation":[{"name":"Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anwar A.","family":"Sayed","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Taibah University, Medina, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Hematology, Shandong Province Hospital, Shandong First Medical University, Jinan, China, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle M.H.","family":"Tan","sequence":"additional","affiliation":[{"name":"Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9571-0819","authenticated-orcid":false,"given":"Eleanor","family":"Watt","sequence":"additional","affiliation":[{"name":"Great Ormond Street Hospital for Children, United 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United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7153-2547","authenticated-orcid":false,"given":"Emma V.","family":"Thorley","sequence":"additional","affiliation":[{"name":"Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3873-1602","authenticated-orcid":false,"given":"Ariam","family":"Teklemichael","sequence":"additional","affiliation":[{"name":"Department of Haematology, Hammersmith Hospital, Imperial Health Care NHS Trust, London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunchuan","family":"Ding","sequence":"additional","affiliation":[{"name":"Imperial College London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice 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