Targeting of tumor cells for human gammadelta T cells by nonpeptide antigens.
Human Vgamma2/Vdelta2(+) gammadelta T cells respond to low molecular-mass nonpeptide Ags in a gammadelta TCR-dependent manner. Although requirements of Ag presentation have remained controversial, we have indicated that specific responses of the primary gammadelta 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 gammadelta T cells, inducing specific proliferation and IFN-gamma production. gammadelta TCR dependency of the response to Ag-pulsed tumor cells was confirmed by using a Jurkat line transfected with a Vgamma2/Vdelta2 gammadelta TCR. Furthermore, gammadelta 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 gammadelta 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 gammadelta T cells but also may provide a novel strategic clue for immunotherapy of human malignancy.
Kato
Y
Y
Department of Immunology and Cell Biology, Graduate School of Biostudies, and Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Tanaka
Y
Y
Miyagawa
F
F
Yamashita
S
S
Minato
N
N
D003602:Cytotoxicity, Immunologic; D011756:Diphosphates / Q000494:pharmacology*; D004164:Diphosphonates / Q000494:pharmacology*; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D000077268:Pamidronate; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D011756:Diphosphates; D004164:Diphosphonates; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma; D000077268:Pamidronate