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 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, with a decrease in IL-10 levels. 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.

脓毒症期间或严重外伤后可能发生免疫功能障碍。单核细胞HLA-DR表达减少和细胞因子反应与死亡率相关。最近的研究表明，这种患者也可能发生适应性免疫系统缺陷，其特征在于PD-L1表达增加和相关的T细胞无反应性。这项研究的目的是确定免疫佐剂干扰素-γ对人离体全血感染模型中单核细胞PD-L1表达和T细胞活化的影响。我们发现，用干扰素-γ处理后，单核细胞响应LPS刺激而增加了HLA-DR表达并增加了TNF-α的产生，并降低了IL-10的水平。LPS和干扰素-γ均可增加单核细胞PD-L1表达水平，通过流式细胞术测定，两种药物的组合可协同刺激PD-L1水平的进一步增加。然而，尽管PD-L1表达升高，但通过添加干扰素-γ治疗并没有减弱CD4和CD8 T细胞的活化。这些发现表明，PD-L1可能不是T细胞无反应性的可靠标志物，并且干扰素-γ仍然是令人感兴趣的佐剂，可以改善单核细胞的炎症反应，同时保留T细胞活化。