Human V Gamma 9v Delta 2 T Cells Specifically Recognize And Kill Acute Myeloid Leukemic Blasts

V gamma 9V delta 2 T cells are attractive candidates for antileukemic activity. The analysis of V gamma 9V delta 2 T cells in newly diagnosed acute myeloid leukemia (AML) patients revealed that their absolute cell numbers were normal in the blood as well as in the bone marrow but showed a striking imbalance in the differentiation subsets, with preponderance of the effector memory population. This unusual phenotype was restored after removal of leukemic cells in patients, which reached complete remission after chemotherapy, suggesting that leukemic cells might be involved in the alteration of gamma delta T cell development in AML. Accordingly, coculture between AML cells and V gamma 9V delta 2 T cells induced selection of effector cells. In accordance with their effector memory status, in vitro proliferation of V gamma 9V delta 2 T cells was reduced compared with normal controls. Nevertheless, V gamma 9V delta 2 T cells efficiently killed autologous AML blasts via the perforin/granzyme pathway. The ligands for DNAM-1 were expressed by AML cells. We showed that killing of AML blasts was TCR and DNAM-1 dependent. Using a xenotransplantation murine model, we showed that V gamma 9V delta 2 T cells homed to the bone marrow in close proximity of engrafted leukemic cells and enhanced survival. These data demonstrate that V gamma 9V delta 2 T cells are endowed with the ability to interact with and eradicate AML blasts both in vitro and in a mouse model. Collectively, our data revealed that V gamma 9V delta 2 T cells have a potent antileukemic activity provided that optimal activation is achieved, such as with synthetic TCR agonists. This study enhances the interest of these cells for therapeutic purposes such as AML treatment. The Journal of Immunology, 2012, 188: 4701-4708.