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

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.