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) |