Divergent roles for antigenic drive in the aetiology of primary versus dasatinib-associated CD8+ TCR-Vβ+ expansions.
Anna LissinaJames E McLarenMette IlanderEmma I AnderssonCatherine S LewisMathew ClementAndrew HermanKristin LadellSian Llewellyn-LaceyKelly L MinersEmma GostickJ Joseph MelenhorstA John BarrettDavid A PriceSatu MustjokiLinda WooldridgePublished in: Scientific reports (2018)
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.
Keyphrases
- end stage renal disease
- regulatory t cells
- newly diagnosed
- ejection fraction
- rheumatoid arthritis
- chronic kidney disease
- drug induced
- peritoneal dialysis
- prognostic factors
- acute myeloid leukemia
- bone marrow
- chronic myeloid leukemia
- systemic lupus erythematosus
- affordable care act
- immune response
- dendritic cells
- patient reported
- disease activity