Enhancement of Anti-tumor Cytotoxicity of Expanded gamma delta T Cells by Stimulation with Monocyte-derived Dendritic Cells

In order to establish the method of generating powerful gd T cells for anti-tumor immunotherapy, we investigated the effects of monocyte-derived dendritic cells (mo-DCs) on anti-tumor cytotoxicity of expanded gamma delta T cells. Activation of gamma delta T cells co-cultured for 2-3da ys with immature or mature mo-DCs was evaluated by CD69 expression and anti-tumor cytotoxicity using two assays : the 5-(and 6-) carboxyfluorescein diacetate, succinimidyl ester-based cytotoxicity assay and the calcein-AM-based Terascan assay. gamma delta T cells were used as effector cells and myeloma cell line (RPMI8226) or chronic myelogenous leukemia blastic crisis cell line (C2F8) were used as target cells. CD69 expression on gamma delta T cells was enhanced by co-culture with both immature and mature mo-DCs in a cell-number-dependent fashion. CD69 expression was enhanced after addition of mo-DCs of either autologous or allogeneic origin. Activation of gamma delta T cells with mo-DCs enhanced anti-tumor cytotoxicity of gamma delta T cells against RPMI8226 and C2F8 in an effector-to-target ratio-dependent manner. Activation of gamma delta T cells by mo-DCs was associated with the enhancement of anti-tumor cytotoxicity of gamma delta T cells. Potent gamma delta T cells activated by mo-DCs were considered to be applicable to an efficient gamma delta T cell-mediated immunotherapy for tumors.