2024-03-29T08:33:15Z
https://u-ryukyu.repo.nii.ac.jp/oai
oai:u-ryukyu.repo.nii.ac.jp:02012193
2023-08-03T05:31:07Z
1642838163960:1642838338003
1642838403551:1642838407795
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
Rowan, Aileen G.
Witkover, Aviva
Melamed, Anat
Tanaka, Yuetsu
Cook, Lucy B. M.
Fields, Paul
Taylor, Graham P.
Bangham, Charles R. M.
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.
論文
http://purl.org/coar/resource_type/c_6501
Public Library of Science
2016-11-28
VoR
http://hdl.handle.net/20.500.12000/45207
1553-7366
1553-7374
AA12072310
PLoS Pathogens
11
12
20
1
eng
https://doi.org/10.1371/journal.ppat.1006030
10.1371/journal.ppat.1006030
open access