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Cytotherapy. 2012 Oct;14(9):1110-8. doi: 10.3109/14653249.2012.700766. Epub 2012 Jul 17.

Human Vdelta1 gamma-delta T cells exert potent specific cytotoxicity against primary multiple myeloma cells.

Author information

1
Department of Haematology, Royal Free Hospital, University College Medical School London, UK. a.knight@medsch.ucl.ac.uk

Abstract

BACKGROUND AIMS:

Human gamma-delta (γδ) T cells are potent effector lymphocytes of innate immunity involved in anti-tumor immune surveillance. However, the Vδ1 γδ T-cell subset targeting multiple myeloma (MM) has not previously been investigated.

METHODS:

Vδ1 T cells were purified from peripheral blood mononuclear cells of healthy donors and patients with MM by immunomagnetic sorting and expanded with phytohemagglutinin (PHA) together with interleukin (IL)-2 in the presence of allogeneic feeders. Vδ1 T cells were phenotyped by flow cytometry and used in a 4-h flow cytometric cytotoxicity assay. Cytokine release and blocking studies were performed. Primary myeloma cells were purified from MM patients' bone marrow aspirates.

RESULTS:

Vδ1 T cells expanded from healthy donors displayed prominent cytotoxicity by specific lysis against patients' CD38 (+) CD138 (+) bone marrow-derived plasma cells. Vδ1 T cells isolated from MM patients showed equally significant killing of myeloma cells as Vδ1 T cells from normal donors. Vδ1 T cells showed similarly potent cytotoxicity against myeloma cell lines U266 and RPMI8226 and plasma cell leukemia ARH77 in a dose-dependent manner. The interferon (IFN)-γ secretion and Vδ1 T-cell cytotoxicity against myeloma cells was mediated in part through the T-cell receptor (TCR) in addition to involvement of Natural killer-G2D molecule (NKG2D), DNAX accessory molecule-1 (DNAM-1), intracellular cell adhesion molecule (ICAM)-1, CD3 and CD2 receptors. In addition, Vδ1 T cells were shown to exert anti-myeloma activity equal to that of Vδ2 T cells.

CONCLUSIONS:

We have shown for the first time that Vδ1 T cells are highly myeloma-reactive and have therefore established Vδ1 γδ T cells as a potential candidate for a novel tumor immunotherapy.

PMID:
22800570
DOI:
10.3109/14653249.2012.700766
[Indexed for MEDLINE]

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