title: T Cell Receptor Vβ Staining Identifies the Malignant Clone in Adult T cell Leukemia and Reveals Killing of Leukemia Cells by Autologous CD8+ T cells.
abstract: There is growing evidence that CD8+ cytotoxic T lymphocyte (CTL) responses can contribute to long-term remission of many malignancies. The etiological agent of adult T-cell leukemia/lymphoma (ATL), human T lymphotropic virus type-1 (HTLV-1), contains highly immunogenic CTL epitopes, but ATL patients typically have low frequencies of cytokine-producing HTLV-1-specific CD8+ cells in the circulation. It remains unclear whether patients with ATL possess CTLs that can kill the malignant HTLV-1 infected clone. Here we used flow cytometric staining of TCRVβ and cell adhesion molecule-1 (CADM1) to identify monoclonal populations of HTLV-1-infected T cells in the peripheral blood of patients with ATL. Thus, we quantified the rate of CD8+-mediated killing of the putative malignant clone in ex vivo blood samples. We observed that CD8+ cells from ATL patients were unable to lyse autologous ATL clones when tested directly ex vivo. However, short in vitro culture restored the ability of CD8+ cells to kill ex vivo ATL clones in some donors. The capacity of CD8+ cells to lyse HTLV-1 infected cells which expressed the viral sense strand gene products was significantly enhanced after in vitro culture, and donors with an ATL clone that expressed the HTLV-1 Tax gene were most likely to make a detectable lytic CD8+ response to the ATL cells. We conclude that some patients with ATL possess functional tumour-specific CTLs which could be exploited to contribute to control of the disease.
authors.affiliation: Section of Virology, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Aileen G
authors.identifier: http://orcid.org/0000-0002-7897-1814
authors.initials: AG
authors.lastname: Rowan
authors.affiliation: Section of Virology, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Aviva
authors.initials: A
authors.lastname: Witkover
authors.affiliation: Section of Virology, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Anat
authors.identifier: http://orcid.org/0000-0002-7312-3138
authors.initials: A
authors.lastname: Melamed
authors.affiliation: Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Section of Virology, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Lucy B M
authors.identifier: http://orcid.org/0000-0003-2422-4642
authors.initials: LB
authors.lastname: Cook
authors.affiliation: Guy's and St Thomas' Hospital, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Fields
authors.affiliation: Section of Virology, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Graham P
authors.identifier: http://orcid.org/0000-0002-3773-2390
authors.initials: GP
authors.lastname: Taylor
authors.affiliation: Section of Virology, Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Charles R M
authors.initials: CR
authors.lastname: Bangham
mesh_terms: D000328:Adult; D000368:Aged; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D016356:Gene Products, tax / Q000276:immunology; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D016356:Gene Products, tax; D016693:Receptors, Antigen, T-Cell, alpha-beta