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

Background aims. Human gamma-delta (gamma delta) T cells are potent effector lymphocytes of innate immunity involved in anti-tumor immune surveillance. However, the V delta 1 gamma delta T-cell subset targeting multiple myeloma (MM) has not previously been investigated. Methods. V delta 1 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. V delta 1 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. V delta 1 T cells expanded from healthy donors displayed prominent cytotoxicity by specific lysis against patients' CD38(+) CD138(+) bone marrow-derived plasma cells. V delta 1 T cells isolated from MM patients showed equally significant killing of myeloma cells as V delta 1 T cells from normal donors. V delta 1 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)-gamma secretion and V delta 1 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, V delta 1 T cells were shown to exert anti-myeloma activity equal to that of V delta 2 T cells. Conclusions. We have shown for the first time that V delta 1 T cells are highly myeloma-reactive and have therefore established V delta 1 gamma delta T cells as a potential candidate for a novel tumor immunotherapy.