Open AccessT Cell Receptor Vβ Staining Identifies the Malignant Clone in Adult T cell Leukemia and Reveals Killing of Leukemia Cells by Autologous CD8+ T cells
Author(s) -
Aileen Rowan,
Aviva Witkover,
Anat Melamed,
Yuetsu Tanaka,
Lucy Cook,
Paul Fields,
Graham P. Taylor,
Charles R. M. Bangham
Publication year - 2016
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1006030
Subject(s) - cytotoxic t cell , clone (java method) , biology , cd8 , t cell leukemia , leukemia , ex vivo , virology , immunology , ctl* , in vivo , in vitro , immune system , gene , biochemistry , microbiology and biotechnology
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.