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.

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Activated T cells played critical roles in immunotherapy and adoptive T cell therapy, and a non-invasive imaging strategy can provide us useful information concerning the transportation, accumulation, and homing of T cells in vivo. In this paper, by utilizing the long half-life radionuclide iodine-124 (124I) and CD25 specific monoclonal antibody Basiliximab, we have fabricated a novel probe, namely, 124I-Basiliximab, which was highly promising in the immuno-PET imaging of T cells. In vitro, 124I-Basiliximab had superior affinity to CD25 protein (Kd = 5.31 nM) and exhibited much higher accumulation in CD25 high-expression lymphoma cell line Karpas299 than that in CD25-negative cell line Daudi. In vivo, 124I-Basiliximab was excreted slowly from the body of mice, rendering it a relatively high effective dose (0.393 mSv/MBq) when applied in the immuno-PET imaging. In Karpas299 tumor xenograft, 124I-Basiliximab probe was observed to accumulate in the tumor quickly after tracer administration, with the optimal image acquired at 24 h post-injection. More importantly, PHA-activated hPBMC had much higher uptake of 124I-Basiliximab, indicating the potential utility of 124I-Basiliximab to discriminate activated hPBMC from its non-activated status. In summary, 124I-Basiliximab was fabricated for the first time, which can be applied in CD25-targeted immuno-PET imaging of activated T cells in vivo.