Loacker et al.: "PD-L1 Overexpression Following COVID Vaccination"; Increased PD-L1 surface expression on peripheral blood granulocytes and monocytes after vaccination with SARS-CoV2 mRNA or vector

vaccine; evidence suggests that PD-L1 upregulation after vaccination may correlate with some vaccination side-effects

‘The immune response is accompanied by the activation of a highly complex network of immune activator and inhibitor pathways. Immune defense reactions coexist with reactions maintaining self-tolerance and the balance between these processes is crucial.

Immune checkpoints play an important role in controlling this network. Inhibitory immune checkpoint molecules minimize collateral tissue damage and are essential for the prevention of autoimmune diseases [1].

One important inhibitory checkpoint receptor is programmed cell death protein 1 (PD-1, CD279) which is typically found on T cells and also on other cells like mature B-cells [2]. Its ligands, programmed death-ligand 1 (PD-L1) and PD-L2, are regularly expressed on antigen presenting cells like dendritic cells and macrophages; upregulation of PD-L1 is observed after activation of monocytes and granulocytes [3, 4].’

Researchers were ‘interested to know whether vaccine-induced activation of the immune system also causes measurable regulating effects, for instance an increase in PD-L1 expression. As part of a large ongoing vaccination study [6], we therefore compared the PD-L1 expression on peripheral blood monocytes and granulocytes of healthy vaccinated probands and of a not vaccinated control group.’

Why is it important to understand the role of PD-L1 upregulation or elevation?

‘The significance of PD-L1 expression following immunization is currently unknown. Upregulation of PD-L1 might merely reflect the physiological immune regulation, but on the other hand it could also influence the outcome of vaccinations or the incidence and type of side effects.

Indeed, a recently published case report suggests that PD-L1 upregulation after vaccination may correlate with some vaccination side-effects [8]’.

For example, Jiang et al. looked at the role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape.

Jiang et al. reported that ‘the programmed death ligand-1/programmed death-1 (PD-L1/PD-1) signaling pathway is an important component of tumor immunosuppression, which can inhibit the activation of T lymphocytes and enhance the immune tolerance of tumor cells, thereby achieving tumor immune escape.’

Re-focusing on the research by Loacker et al., the results showed that PD-L1 expression of peripheral granulocytes & monocytes of vaccinated individuals is significantly higher than the expression found in non-vaccinated persons.

‘Results demonstrate a statistically significant (p<0.01) increase in PD-L1 expression both on peripheral granulocytes and monocytes of the vaccinated individuals (Figure 1; median delta mean fluorescence intensity [MFI] 1.71 and 2.26, respectively) in comparison to the control group of healthy non-vaccinated individuals (median delta MFI 0.65 and 0.51).’

‘The present study shows that the PD-L1 expression of peripheral granulocytes and monocytes of vaccinated individuals is significantly higher than the expression found in non-vaccinated individuals. Furthermore, PD-L1 expression correlates inversely with mitogen-induced T-cell stimulability in the IFN-γ release assay.’

SOURCE:

https://www.degruyter.com/document/doi/10.1515/cclm-2022-0787/html

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