RRC ID 65849
著者 Domae E, Hirai Y, Ikeo T, Goda S, Shimizu Y.
タイトル Cytokine-mediated activation of human ex vivo-expanded Vγ9Vδ2 T cells.
ジャーナル Oncotarget
Abstract Vγ9Vδ2 T cells, the major subset of the human peripheral blood γδ T-cell, respond to microbial infection and stressed cells through the recognition of phosphoantigens. In contrast to the growing knowledge of antigen-mediated activation mechanisms, the antigen-independent and cytokine-mediated activation mechanisms of Vγ9Vδ2 T cells are poorly understood. Here, we show that interleukin (IL) -12 and IL-18 synergize to activate human ex vivo-expanded Vγ9Vδ2 T cells. Vγ9Vδ2 T cells treated with IL-12 and IL-18 enhanced effector functions, including the expression of IFN-γ and granzyme B, and cytotoxicity. These enhanced effector responses following IL-12 and IL-18 treatment were associated with homotypic aggregation, enhanced expression of ICAM-1 and decreased expression of the B- and T-lymphocyte attenuator (BTLA), a co-inhibitory receptor. IL-12 and IL-18 also induced the antigen-independent proliferation of Vγ9Vδ2 T cells. Increased expression of IκBζ, IL-12Rβ2 and IL-18Rα following IL-12 and IL-18 stimulation resulted in sustained activation of STAT4 and NF-κB. The enhanced production of IFN-γ and cytotoxic activity are critical for cancer immunotherapy using Vγ9Vδ2 T cells. Thus, the combined treatment of ex vivo-expanded Vγ9Vδ2 T cells with IL-12 and IL-18 may serve as a new strategy for the therapeutic activation of these cells.
巻・号 8(28)
ページ 45928-45942
公開日 2017-7-11
DOI 10.18632/oncotarget.17498
PII 17498
PMID 28521284
PMC PMC5542238
MeSH Adaptor Proteins, Signal Transducing Cell Proliferation / drug effects Cells, Cultured Cytokines / metabolism* Humans I-kappa B Proteins / genetics Lymphocyte Activation / drug effects* Lymphocyte Activation / immunology* Nuclear Proteins / genetics Receptors, Antigen, T-Cell, gamma-delta / metabolism* T-Lymphocyte Subsets / drug effects* T-Lymphocyte Subsets / physiology*
IF 5.168
リソース情報
ヒト・動物細胞 RPMI8226(RCB3010) MG-63(RCB1890)