Figure 2. Spike protein induction of an inflammatory response. The
events leading to hyper-activation of inflammation can concurrently
occur through (a) a CD4+ T cell over-production via the stimulation of
NIK (the alternative NF-κB pathway) and thereby loss of self-antigen
tolerance, and (b) a promotion of inflammation through the inhibition of
IRF3 and type I IFN, and subsequent impairment of mTOR activity.
[111,116,153,158,159,161,162].
11. TGF-β Signalling and the Development of a Th17 Response
In the remarkable work of Liu L et al. [33], the responses of immune
cells to the inactivated SARS-CoV-2 vaccine, as shown in Table 1, cause
enhanced TGF-β signalling. This is in addition to the increased NF-kB
response. This is enhanced only in some subtypes of immune cells.
Specifically, the CD4+ Treg cells, CD4+ T proliferative cells, monocytes
and dendritic cells show intense TGF-β signalling. These immune cells
have roles that impact the efficient control and development of Treg
responses [3]. Furthermore, intense TGF-β signalling and increased
IL-6 and TNF-α expression are observed when the immune cells encounter
huge amounts of the SARS-CoV-2 mRNA coded spike protein in vaccinated
individuals [163].
As shown in Table 1, the T cell subsets (including the Treg cells) that
show intense TGF-β signalling are also resistant to hypoxia effects. For
the Τ cells to sustain themselves in this environment, they likely
express adequate hypoxia inducible factors (HIFs). Moreover, HIF has
been shown to be protective against uptake of the spike protein through
multiple mechanisms [164].
Table 1. The hypoxia effect, and TGF-β signalling responses of
progenitor lineages of immune cell subsets to the inactivated SARS-CoV-2
vaccine containing the spike protein mRNA. Adapted from Liu et
al., 2021 [33].