Expression and function of PD-1 in human γδ T cells that recognize phosphoantigens.
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.
Laboratory of Immunology and Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
Masashi
M
Iwasaki
Yoshimasa
Y
Tanaka
Hirohito
H
Kobayashi
Kaoru
K
Murata-Hirai
Hideto
H
Miyabe
Tomoharu
T
Sugie
Masakazu
M
Toi
Nagahiro
N
Minato
D000941:Antigens / Q000276:immunology*; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D060890:B7-H1 Antigen; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D011756:Diphosphates / Q000276:immunology; D004164:Diphosphonates / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000276:immunology / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D009943:Organophosphorus Compounds / Q000276:immunology* / Q000494:pharmacology; D061026:Programmed Cell Death 1 Receptor; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D000077211:Zoledronic Acid
C443995:4-hydroxy-3-methylbut-2-enyl pyrophosphate; D000941:Antigens; D015703:Antigens, CD; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D016207:Cytokines; D011756:Diphosphates; D004164:Diphosphonates; D007093:Imidazoles; D007376:Interleukin-2; D009943:Organophosphorus Compounds; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000077211:Zoledronic Acid; D007371:Interferon-gamma