Cytokine-mediated activation of human ex vivo-expanded Vγ9Vδ2 T cells

Eisuke Domae, Yuya Hirai, Takashi Ikeo, Seiji Goda, Yoji Shimizu

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Vγ9Vδ2 T cells, the major subset of the human peripheral blood γd 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 coinhibitory receptor. IL-12 and IL-18 also induced the antigen-independent proliferation of Vγ9Vδ2 T cells. Increased expression of IκBζ, IL-12Rβ2 and IL-18Ra 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.

Original languageEnglish (US)
Pages (from-to)45928-45942
Number of pages15
JournalOncotarget
Volume8
Issue number28
DOIs
StatePublished - Jan 1 2017

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Interleukin-18
Interleukin-12
Cytokines
T-Lymphocytes
Interleukins
Antigens
Granzymes
T-Lymphocyte Subsets
Intercellular Adhesion Molecule-1
Immunotherapy
Therapeutics
Infection
Neoplasms

Keywords

  • IL-12/IL-18
  • IκBζ
  • STAT4, NF-κB p65
  • γδ T cells

Cite this

Cytokine-mediated activation of human ex vivo-expanded Vγ9Vδ2 T cells. / Domae, Eisuke; Hirai, Yuya; Ikeo, Takashi; Goda, Seiji; Shimizu, Yoji.

In: Oncotarget, Vol. 8, No. 28, 01.01.2017, p. 45928-45942.

Research output: Contribution to journalArticle

Domae, Eisuke ; Hirai, Yuya ; Ikeo, Takashi ; Goda, Seiji ; Shimizu, Yoji. / Cytokine-mediated activation of human ex vivo-expanded Vγ9Vδ2 T cells. In: Oncotarget. 2017 ; Vol. 8, No. 28. pp. 45928-45942.
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