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

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.

journal_name

Cytotherapy

journal_title

Cytotherapy

authors

Knight A,Mackinnon S,Lowdell MW

doi

10.3109/14653249.2012.700766

subject

Has Abstract

pub_date

2012-10-01 00:00:00

pages

1110-8

issue

9

eissn

1465-3249

issn

1477-2566

pii

S1465-3249(12)71229-X

journal_volume

14

pub_type

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