Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 41, Issue 2, Pages 345-355Publisher
WILEY
DOI: 10.1002/eji.201040959
Keywords
gamma delta T cells; Phosphoantigen; PD-1; PD-L1; Tumor
Categories
Funding
- Ministry of Education, Science, Culture, Sports, and Technology of Japan (MEXT)
- Astellas Pharma Inc.
- Formation of Center for Innovation
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Programmed cell death-1 (PD-1) is an inhibitory receptor and plays an important role in the regulation of alpha beta T cells. Little is known, however, about the role of PD-1 in gamma delta T cells. In this study, we investigated the expression and function of PD-1 in human gamma delta T cells. Expression of PD-1 was rapidly induced in primary gamma delta T cells following antigenic stimulation, and the PD-1(+) gamma delta T cells produced IL-2. When PD-1(+) gamma delta T cells were stimulated with Daudi cells with and without programmed cell death ligand-1 (PD-L1) expression, the levels of IFN-gamma 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-L1(+) gamma delta T cells were challenged by PD-L1(+) tumors pretreated with zoledronate (Zol), which induced gamma delta TCR-mediated signaling, the resulting reduction in cytokine production was only slight to moderate compared to the reduction seen when PD-L1(+) gamma delta T cells were challenged by PD-L1(-) tumors. In addition, cytotoxic activity of PD-L1(+) gamma delta 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 gamma delta T cells.
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