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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
Authors :Rowan, Aileen G.
Witkover, Aviva
Melamed, Anat
Tanaka, Yuetsu
Cook, Lucy B. M.
Fields, Paul
Taylor, Graham P.
Bangham, Charles R. M.
Issue Date :28-Nov-2016
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 CD^8+ 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.
URL :https://doi.org/10.1371/journal.ppat.1006030
Type Local :雑誌掲載論文
ISSN :1553-7366
Publisher :Public Library of Science
URI :http://hdl.handle.net/20.500.12000/45207
Citation :PLoS Pathogens Vol.12 no.11 p.1 -20
Appears in Collections:Peer-reviewed Journal Articles (Faculty of Medicine)

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