Lissina, Anna, McLaren, James E., Ilander, Mette, Andersson, Emma I., Lewis, Catherine S., Clement, Mathew, Herman, Andrew, Ladell, Kristin, Llewellyn-Lacey, Sian, Miners, Kelly L., Gostick, Emma, Melenhorst, J. Joseph, Barrett, A. John, Price, David A., Mustjoki, Satu and Wooldridge, Linda 2018. Divergent roles for antigenic drive in the aetiology of primary versus dasatinib-associated CD8+ TCR-Vβ+ expansions. Scientific Reports 8 (1) , 2534. 10.1038/s41598-017-18062-x |
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Abstract
CD8+ T-cell expansions are the primary manifestation of T-cell large granular lymphocytic leukemia (T-LGLL), which is frequently accompanied by neutropenia and rheumatoid arthritis, and also occur as a secondary phenomenon in leukemia patients treated with dasatinib, notably in association with various drug-induced side-effects. However, the mechanisms that underlie the genesis and maintenance of expanded CD8+ T-cell receptor (TCR)-Vβ+ populations in these patient groups have yet to be fully defined. In this study, we performed a comprehensive phenotypic and clonotypic assessment of expanded (TCR-Vβ+) and residual (TCR-Vβ−) CD8+ T-cell populations in T-LGLL and dasatinib-treated chronic myelogenous leukemia (CML) patients. The dominant CD8+ TCR-Vβ+ expansions in T-LGLL patients were largely monoclonal and highly differentiated, whereas the dominant CD8+ TCR-Vβ+ expansions in dasatinib-treated CML patients were oligoclonal or polyclonal, and displayed a broad range of memory phenotypes. These contrasting features suggest divergent roles for antigenic drive in the immunopathogenesis of primary versus dasatinib-associated CD8+ TCR-Vβ+ expansions.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Medicine |
Publisher: | Nature Publishing Group |
ISSN: | 2045-2322 |
Funders: | Wellcome Trust, Bloodwise European Research Council |
Date of First Compliant Deposit: | 15 February 2018 |
Date of Acceptance: | 19 November 2017 |
Last Modified: | 26 Apr 2020 13:40 |
URI: | https://orca.cardiff.ac.uk/id/eprint/109134 |
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