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

Eur J Immunol. 2011 Feb;41(2):345-55. doi: 10.1002/eji.201040959. Epub 2011 Jan 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens / immunology*
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Antigens, Surface / metabolism
  • Apoptosis Regulatory Proteins / metabolism*
  • B7-H1 Antigen
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Cytotoxicity, Immunologic / drug effects
  • Cytotoxicity, Immunologic / immunology
  • Diphosphates / immunology
  • Diphosphonates / immunology
  • Diphosphonates / pharmacology
  • Humans
  • Imidazoles / immunology
  • Imidazoles / pharmacology
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Jurkat Cells
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Organophosphorus Compounds / immunology*
  • Organophosphorus Compounds / pharmacology
  • Programmed Cell Death 1 Receptor
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Zoledronic Acid


  • 4-hydroxy-3-methylbut-2-enyl pyrophosphate
  • Antigens
  • Antigens, CD
  • Antigens, Surface
  • Apoptosis Regulatory Proteins
  • B7-H1 Antigen
  • CD274 protein, human
  • Cytokines
  • Diphosphates
  • Diphosphonates
  • Imidazoles
  • Interleukin-2
  • Organophosphorus Compounds
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, Antigen, T-Cell, gamma-delta
  • Zoledronic Acid
  • Interferon-gamma