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: | 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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