title: Human Vγ9Vδ2 T cells specifically recognize and kill acute myeloid leukemic blasts.
abstract: Vγ9Vδ2 T cells are attractive candidates for antileukemic activity. The analysis of Vγ9Vδ2 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 γδ T cell development in AML. Accordingly, coculture between AML cells and Vγ9Vδ2 T cells induced selection of effector cells. In accordance with their effector memory status, in vitro proliferation of Vγ9Vδ2 T cells was reduced compared with normal controls. Nevertheless, Vγ9Vδ2 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 Vγ9Vδ2 T cells homed to the bone marrow in close proximity of engrafted leukemic cells and enhanced survival. These data demonstrate that Vγ9Vδ2 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 Vγ9Vδ2 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.
authors.affiliation: Institut Paoli-Calmettes, Laboratoire d'Immunologie des Tumeurs, Marseille F-13009, France. j.gertner-dardenne@hotmail.fr
authors.forename: Julie
authors.initials: J
authors.lastname: Gertner-Dardenne
authors.forename: Remy
authors.initials: R
authors.lastname: Castellano
authors.forename: Emilie
authors.initials: E
authors.lastname: Mamessier
authors.forename: Slaveia
authors.initials: S
authors.lastname: Garbit
authors.forename: Eloïse
authors.initials: E
authors.lastname: Kochbati
authors.forename: Anne
authors.initials: A
authors.lastname: Etienne
authors.forename: Aude
authors.initials: A
authors.lastname: Charbonnier
authors.forename: Yves
authors.initials: Y
authors.lastname: Collette
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
authors.forename: Daniel
authors.initials: D
authors.lastname: Olive
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000276:immunology; D001752:Blast Crisis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000276:immunology; D053804:Granzymes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental; D054353:Perforin / Q000276:immunology / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014183:Transplantation, Heterologous; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054353:Perforin; D053804:Granzymes