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

Lissina, Anna, McLaren, James E. ORCID: https://orcid.org/0000-0002-7021-5934, Ilander, Mette, Andersson, Emma I., Lewis, Catherine S., Clement, Mathew ORCID: https://orcid.org/0000-0002-9280-5281, Herman, Andrew, Ladell, Kristin ORCID: https://orcid.org/0000-0002-9856-2938, Llewellyn-Lacey, Sian, Miners, Kelly L., Gostick, Emma, Melenhorst, J. Joseph, Barrett, A. John, Price, David A. ORCID: https://orcid.org/0000-0001-9416-2737, 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:	20 Feb 2024 17:13
URI:	https://orca.cardiff.ac.uk/id/eprint/109134

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