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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.|
Cook, Lucy B. M.
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.|
|Type Local ||:||雑誌掲載論文|
|Publisher ||:||Public Library of Science|
|Citation ||:||PLoS Pathogens Vol.12 no.11 p.1 -20|
|Appears in Collections||:||Peer-reviewed Journal Articles (Faculty of Medicine)|
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