PD-L1 expression induced by the 2009 pandemic influenza A(H1N1) virus impairs the human T cell response

PD-L1 expression plays a critical role in the impairment of T cell responses during chronic infections; however, the expression of PD-L1 on T cells during acute viral infections, particularly during the pandemic influenza virus (A(H1N1)pdm09), and its effects on the T cell response have not been widely explored. We found that A(H1N1)pdm09 virus induced PD-L1 expression on human dendritic cells (DCs) and T cells, as well as PD-1 expression on T cells. PD-L1 expression impaired the T cell response against A(H1N1)pdm09 by promoting CD8+T cell death and reducing cytokine production. Furthermore, we found increased PD-L1 expression on DCs and T cells from influenza-infected patients from the first and second 2009 pandemic waves in Mexico City. PD-L1 expression on CD8+T cells correlated inversely with T cell proportions in patients infected with A(H1N1)pdm09. Therefore, PD-L1 expression on DCs and T cells could be associated with an impaired T cell response during acute infection with A(H1N1)pdm09 virus.

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Activity of Negative Regulation of the PD-1/PD-L1/PD-L2 T-Cell Response System in Patients with Pneumonia and Inﬂuenza A (H1N1)

General Reanimatology ◽

10.15360/1813-9779-2021-4-4-11 ◽

2021 ◽

Vol 17 (4) ◽

pp. 4-11

Author(s):

A. V. Malyarchikov ◽

K. G. Shаpovаlov ◽

S. A. Lukyanov ◽

P. P. Tereshkov ◽

L. S. Kazantseva

Keyword(s):

T Cell ◽

Cell Response ◽

Plasma Levels ◽

Influenza A ◽

Severe Pneumonia ◽

T Cell Response ◽

Negative Regulation ◽

Regulation System ◽

Flow Cytofluorometry ◽

Influenza A H1n1

Systemic inﬂammation is an integral pathophysiological component of many critical illnesses. The systemic inﬂammatory response is based on a cascade of interactions leading to hypercytokinemia and, as a consequence, multiple organ failure, which is one of the main causes of mortality in intensive care units.Aim of the study. To evaluate the activity of the negative regulation system of T-cell response by determining the plasma levels of PD-1, PD-L1 and PD-L2 molecules in pneumonia patients with inﬂuenza A (H1N1).Materials and methods. 85 patients with pneumonia and underlying inﬂuenza A (H1N1) were examined. Among them there were 30 patients with severe pneumonia, and 55 patients with non-severe pneumonia. Plasma levels of PD-1, PD-L1, PD-L2 molecules was determined by ﬂow cytoﬂuorometry method.Results. In patients with severe pneumonia and underlying inﬂuenza A (H1N1), the plasma level of PD-1 receptor increased 4.6-fold, while the concentration of its ligands PD-L1 and PD-L2 increased 10.6 and 2.2-fold, respectively.Conclusion. Signiﬁcant increase in levels of PD-1 and its ligands PD-L1 and PD-L2 in patients with pneumonia and underlying inﬂuenza A (H1N1) indicates the involvement of negative regulation system of T-cell response in the cascade of immunological reactions and is associated with the severe disease. Possible correction of immune reactions realized through PD-1/PD-L1/PD-L2 complex in critically ill patients is a promising research avenue.

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