Effect of IL-18 on expansion of gammadelta T cells stimulated by zoledronate and IL-2.
Zoledronate (Zol) has recently been shown to expand gammadelta T cells that play important roles in host defenses against infection and tumors. In this study, we examined effects of interleukin-18 (IL-18) on expansion of gammadelta T cells in human peripheral blood mononuclear cells (PBMCs) stimulated by Zol and IL-2. The expansion of gammadelta T cells stimulated by Zol and IL-2 was strongly promoted by exogenous IL-18, and to the contrary, inhibited by neutralizing anti-IL-18 receptor antibody. The gammadelta T cells that expanded in the presence of Zol, IL-2, and IL-18 exhibited the phenotype of effector memory cells characterized by CD44 (+), CD27 (-), and CD45RA (-). In addition, they expressed NKG2D, perforin, CD94, CD25, and CD122, and 15% to 40% of them were positive for CD56. Incubation of gammadelta T cells in the presence with IL-18 produced GM-CSF, IFN-gamma, and TNF-alpha at much higher levels than those incubated without IL-18. They showed strong cytotoxicity against tumor cells including mesothelioma cells and inhibited growth of xenograft of mesothelioma in mice. These observations indicate that IL-18 can efficiently promote expansion of gammadelta T cells with potent antitumor activity.
Li
Wen
W
Institute for Advanced Medical Sciences, Kobe, Japan.
Kubo
Shuji
S
Okuda
Akico
A
Yamamoto
Hideyuki
H
Ueda
Haruyasu
H
Tanaka
Toshiyuki
T
Nakamura
Hideji
H
Yamanishi
Hiromichi
H
Terada
Nobuyuki
N
Okamura
Haruki
H
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004164:Diphosphonates / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D056945:Hep G2 Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D016130:Immunophenotyping; D020382:Interleukin-18 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008654:Mesothelioma / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D053724:Receptors, Interleukin-18 / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000077211:Zoledronic Acid
D000906:Antibodies; D050071:Bone Density Conservation Agents; D016207:Cytokines; D004164:Diphosphonates; D007093:Imidazoles; D020382:Interleukin-18; D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D053724:Receptors, Interleukin-18; D000077211:Zoledronic Acid