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The Journal of Immunology, 2001, 167: 5092-5098.
Copyright © 2001 by The American Association of Immunologists

Targeting of Tumor Cells for Human {gamma}{delta} T Cells by Nonpeptide Antigens1

Yu Kato, Yoshimasa Tanaka, Fumi Miyagawa, Seiji Yamashita and Nagahiro Minato2

Department of Immunology and Cell Biology, Graduate School of Biostudies, and Graduate School of Medicine, Kyoto University, Kyoto, Japan

Human V{gamma}2/V{delta}2+ {gamma}{delta} T cells respond to low molecular-mass nonpeptide Ags in a {gamma}{delta} TCR-dependent manner. Although requirements of Ag presentation have remained controversial, we have indicated that specific responses of the primary {gamma}{delta} T cells to pamidronate were dependent on monocytic adherent cells for Ag presentation. Here, we show that human tumor cells can efficiently present aminobisphosphonate and pyrophosphomonoester compounds to {gamma}{delta} T cells, inducing specific proliferation and IFN-{gamma} production. {gamma}{delta} TCR dependency of the response to Ag-pulsed tumor cells was confirmed by using a Jurkat line transfected with a V{gamma}2/V{delta}2 {gamma}{delta} TCR. Furthermore, {gamma}{delta} T cells exhibited markedly enhanced cytotoxicity against the Ag-pulsed tumor cells as compared with untreated tumor cells. Survey of a number of human tumor cell lines of different origins revealed that the majority of them became susceptible for {gamma}{delta} T cell-mediated cytotoxicity following the Ag pulsing except for breast cancer lines so far examined, while normal PHA blast cells remained resistant. The results not only imply a unique mode of nonpeptide Ag recognition by human {gamma}{delta} T cells but also may provide a novel strategic clue for immunotherapy of human malignancy.




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