In:
Immunology, Wiley, Vol. 142, No. 4 ( 2014-08), p. 551-561
Abstract:
Programmed death‐ligand 1 ( PD ‐ L 1) blockade is accepted as a novel strategy for the reactivation of exhausted T cells that express programmed death‐1 ( PD ‐1). However, the mechanism of PD ‐ L 1‐mediated inhibitory signalling after PD ‐ L 1 cross‐linking by anti‐ PD ‐ L 1 monoclonal antibody (m A b) or PD ‐1–immunogloblin fusion protein ( PD ‐1‐ I g) is still unknown, although it may induce cell death of PD ‐ L 1 + cells required for regular immune reactions. In this study, PD ‐1‐Ig or anti‐ PD ‐L1 m A b treatment was tested in cell lines that expressed PD ‐ L 1 and bovine lymphocytes to investigate whether the treatment induces immune reactivation or PD ‐ L 1‐mediated cell death. PD ‐ L 1 cross‐linking by PD ‐1‐ I g or anti‐ PD ‐ L 1 mA b primarily increased the number of dead cells in PD ‐ L 1 high cells, but not in PD ‐ L 1 low cells; these cells were prepared from Cos‐7 cells in which bovine PD ‐ L 1 expression was induced by transfection. The PD ‐ L 1‐mediated cell death also occurred in Cos‐7 and HeLa cells transfected with vectors only encoding the extracellular region of PD ‐ L 1. In bovine lymphocytes, the anti‐ PD ‐ L 1 m A b treatment up‐regulated interferon‐ γ (IFN‐ γ ) production, whereas PD ‐1‐Ig treatment decreased this cytokine production and cell proliferation. The IFN‐ γ production in B ‐cell‐depleted peripheral blood mononuclear cells was not reduced by PD ‐1‐Ig treatment and the percentages of dead cells in PD ‐ L 1 + B cells were increased by PD ‐1‐Ig treatment, indicating that PD ‐1‐Ig‐induced immunosuppression in bovine lymphocytes could be caused by PD ‐ L 1‐mediated B ‐cell death. This study provides novel information for the understanding of signalling through PD ‐ L 1.
Type of Medium:
Online Resource
ISSN:
0019-2805
,
1365-2567
DOI:
10.1111/imm.2014.142.issue-4
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2006481-0
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