Enhancement of anti-tumor cytotoxicity of expanded gammadelta T Cells by stimulation with monocyte-derived dendritic cells.
In order to establish the method of generating powerful gammadelta T cells for anti-tumor immunotherapy, we investigated the effects of monocyte-derived dendritic cells (mo-DCs) on anti-tumor cytotoxicity of expanded gammadelta T cells. Activation of gammadelta T cells co-cultured for 2-3 days 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. gammadelta 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 gammadelta 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 gammadelta T cells with mo-DCs enhanced anti-tumor cytotoxicity of gammadelta T cells against RPMI8226 and C2F8 in an effector-to-target ratio-dependent manner. Activation of gammadelta T cells by mo-DCs was associated with the enhancement of anti-tumor cytotoxicity of gammadelta T cells. Potent gammadelta T cells activated by mo-DCs were considered to be applicable to an efficient gammadelta T cell-mediated immunotherapy for tumors.
Laboratory of Hematology and Oncology, Graduate School of Health Sciences, Niigata University, Japan.
Anri
A
Saito
Miwako
M
Narita
Ayumi
A
Yokoyama
Norihiro
N
Watanabe
Nozomi
N
Tochiki
Noriyuki
N
Satoh
Jun
J
Takizawa
Tatsuo
T
Furukawa
Ken
K
Toba
Ichiro
I
Fuse
Yoshifusa
Y
Aizawa
Shohji
S
Shinada
Masuhiro
M
Takahashi
D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000502:physiology*; D009000:Monocytes / Q000166:cytology; D009369:Neoplasms / Q000628:therapy*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000099192:CD69 Antigens