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

Anya Lissina, James E McLaren, Mette Ilander, Emma Andersson, Catherine S Lewis, Mathew Clement, Andrew Herman, Kristin Ladell, Sian Llewellyn-Lacey, Kelly Miners, Emma Gostick, J Joseph Melenhorst, A John Barrett, David A Price, Satu Mustjoki, Linda Wooldridge

Research output: Contribution to journalArticle (Academic Journal)peer-review

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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.
Original languageEnglish
Article number2534
Number of pages12
JournalScientific Reports
Volume8
Issue number1
Early online date7 Feb 2018
DOIs
Publication statusE-pub ahead of print - 7 Feb 2018

Keywords

  • CD8+ T-cells
  • CML
  • dasatinib
  • leukemia
  • T-LGLL

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