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

PLoS Pathogens

Yuetsu Tanaka¹  Paul Fields²  Graham P. Taylor³  Aileen G. Rowan³  Aviva Witkover³  Lucy B. M. Cook³  Charles R. M. Bangham³  Anat Melamed³ 

[1] Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan;Guy’s and St Thomas’ Hospital, London, United Kingdom;Section of Virology, Department of Medicine, Imperial College London, London, United Kingdom

关键词: Cloning;    Cytotoxic T cells;    T cells;    Flow cytometry;    HTLV-1;    Cell staining;    Immune response;    Major histocompatibility complex;   

DOI  :  10.1371/journal.ppat.1006030

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY