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Interferon-gamma increases monocyte PD-L1 but does not diminish T-cell activation
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  • Norman Galbraith,
  • Samuel Walker,
  • Sarah Gardner,
  • Campbell Bishop,
  • Susan Galandiuk,
  • Hiram Polk
Norman Galbraith
Royal Alexandra Hospital
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Samuel Walker
University of Kentucky
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Sarah Gardner
University of Louisville School of Medicine
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Campbell Bishop
University of Louisville School of Medicine
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Susan Galandiuk
University of Louisville School of Medicine
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Hiram Polk
University of Louisville School of Medicine
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Abstract

Immune dysfunction can occur during sepsis or following major trauma. Decreased monocyte HLA-DR expression and cytokine responses are associated with mortality. Recent studies have shown that adaptive immune system defects can also occur in in such patients, characterised by increased PD-L1 expression and associated T-cell anergy. The aim of this study was to determine the effects of an immune adjuvant, interferon-gamma, on monocyte PD-L1 expression and T-cell activation in an ex-vivo human whole blood model of infection. We found that with interferon-gamma treatment, monocytes had increased HLA-DR expression and augmented TNF-α production in response to LPS stimulation. Both LPS and interferon-gamma increased the level of monocyte PD-L1 expression, and that a combination of both agents synergistically stimulated a further increase in PD-L1 levels as measured by flow cytometry. However, despite elevated PD-L1 expression, both CD4 and CD8 T-cell activation was not diminished by the addition of interferon-gamma treatment. These findings suggest that PD-L1 may not be a reliable marker for T-cell anergy, and that interferon-gamma remains an adjuvant of interest that can improve the monocyte inflammatory response while preserving T-cell activation.