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Divergent roles for antigenic drive in the aetiology of primary versus dasatinib-associated CD8+ TCR-Vβ+ expansions

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
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: 31 Mar 2018 20:58
URI: http://orca.cf.ac.uk/id/eprint/109134

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