Type I IFN-mediated enhancement of anti-leukemic cytotoxicity of gammadelta T cells expanded from peripheral blood cells by stimulation with zoledronate.
BACKGROUND
In order to establish efficient gammadelta T-cell based tumor immunotherapy, we explored a method to enhance the cytotoxicity of gammadelta T cells against leukemia cells by stimulating gammadelta T cells with type I IFN.


METHODS
Gammadelta T cells were expanded from normal PBMC by culturing with zoledronate and a low concentration of IL-2 for 2 weeks. For the activation of gammadelta T cells, gammadelta T cells were cultured with type I IFN (HLBI, IFN-alpha2b and IFN-beta) for 1-3 days. The cytotoxicity of HLBI-activated gammadelta T cells against leukemia cell lines and fresh leukemia cells was evaluated by 51Cr-release assay.


RESULTS
Gammadelta T cells, which were expanded and purified with magnetic beads using an anti-gammadelta TCR MAb, were demonstrated to be cytotoxic against leukemia cell lines of both lymphoid and myeloid origin and fresh myeloid leukemia cells. By culturing expanded gammadelta T cells with type I IFN, the expression of the activation marker CD69 was increased and the cytometric bead array showed an elevated production of IFN-gamma by gammadelta T cells. In addition, the cytotoxicity of gammadelta T cells against leukemia cells was definitely enhanced by culturing gammadelta T cells with HLBI.


CONCLUSIONS
The present study has demonstrated that type I IFN could enhance the anti-leukemic cytotoxicity of expanded gammadelta T cells, which implies that in vitro bisphosphonate (such as zoledronate)-expanded and type I IFN-activated gammadelta T cells could be applied to immunotherapy for hematologic malignancies such as leukemia and lymphoma.
Watanabe
N
N
Division of Hematology and Oncology, Graduate School of Health Sciences, Niigata, Japan.
Narita
M
M
Yokoyama
A
A
Sekiguchi
A
A
Saito
A
A
Tochiki
N
N
Furukawa
T
T
Toba
K
K
Aizawa
Y
Y
Takahashi
M
M
D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D016219:Immunotherapy, Adoptive; D007370:Interferon Type I / Q000494:pharmacology* / Q000502:physiology; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000494:pharmacology; D037181:Lectins, C-Type; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000077211:Zoledronic Acid; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D004164:Diphosphonates; D007093:Imidazoles; D007370:Interferon Type I; D007371:Interferon-gamma; D007376:Interleukin-2; D037181:Lectins, C-Type; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000077211:Zoledronic Acid; D000099192:CD69 Antigens