Interferon-gamma increases monocyte PD-L1 but does not diminish T-cell
activation
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.