Expression and function of PD-1 in human γδ T cells that recognize phosphoantigens

Masashi Iwasaki, Yoshimasa Tanaka, Hirohito Kobayashi, Kaoru Murata-Hirai, Hideto Miyabe, Tomoharu Sugie, Masakazu Toi, Nagahiro Minato

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    63 Scopus citations

    Abstract

    Programmed cell death-1 (PD-1) is an inhibitory receptor and plays an important role in the regulation of αβ T cells. Little is known, however, about the role of PD-1 in γδ T cells. In this study, we investigated the expression and function of PD-1 in human γδ T cells. Expression of PD-1 was rapidly induced in primary γδ T cells following antigenic stimulation, and the PD-1+ γδ T cells produced IL-2. When PD-1+ γδ T cells were stimulated with Daudi cells with and without programmed cell death ligand-1 (PD-L1) expression, the levels of IFN-γ production and cytotoxicity in response to PD-L1+ Daudi cells were diminished compared to the levels seen in response to PD-L1- Daudi cells. The attenuated effector functions were reversed by anti-PD-L1 mAb. When PD-1+ γδ T cells were challenged by PD-L1+ tumors pretreated with zoledronate (Zol), which induced γδ TCR-mediated signaling, the resulting reduction in cytokine production was only slight to moderate compared to the reduction seen when PD-1+ γδ T cells were challenged by PD-L1- tumors. In addition, cytotoxic activity of PD-1+ γδ T cells against Zol-treated PD-L1+ tumors was comparable to that against Zol-treated PD-L1- tumors. These results suggest that TCR triggering may partially overcome the inhibitory effect of PD-1 in γδ T cells.

    Original languageEnglish (US)
    Pages (from-to)345-355
    Number of pages11
    JournalEuropean Journal of Immunology
    Volume41
    Issue number2
    DOIs
    StatePublished - Feb 1 2011

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    Keywords

    • PD-1
    • PD-L1
    • Phosphoantigen
    • Tumor
    • γδ T cells

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

    Cite this

    Iwasaki, M., Tanaka, Y., Kobayashi, H., Murata-Hirai, K., Miyabe, H., Sugie, T., Toi, M., & Minato, N. (2011). Expression and function of PD-1 in human γδ T cells that recognize phosphoantigens. European Journal of Immunology, 41(2), 345-355. https://doi.org/10.1002/eji.201040959