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The Health | august-September, 2020
| Covid-19 |
T Cells to the rescue
An enigmatic type of white blood cell
may well prove to be crucial in our fight
against Covid-19
While the latest research
suggests that antibodies
against Covid-19 could be
lost in just three months, a
new hope has appeared on
the horizon: the enigmatic
T cell.
The clues have been mounting for a
while. First, scientists discovered patients
who had recovered from infection with
Covid-19, but mysteriously didn’t have any
antibodies against it. Next it emerged that
this might be the case for a significant
number of people. Then came the finding
that many of those who do develop
antibodies seem to lose them again after
just a few months.
The BBC reported that in short, though
antibodies have proved invaluable for
tracking the spread of the pandemic,
they might not have the leading role in
immunity that we once thought. If we are
going to acquire long-term protection, it
looks increasingly like it might have to
come from somewhere else.
But while the world has been
preoccupied with antibodies, researchers
have started to realise that there might be
another form of immunity – one which, in
some cases, has been lurking undetected
in the body for years. An enigmatic type
of white blood cell is gaining prominence.
And though it hasn’t previously featured
heavily in the public consciousness, it
may well prove to be crucial in our fight
against Covid-19. This could be the T cell’s
big moment.
T cells are a kind of immune cell,
whose main purpose is to identify and
kill invading pathogens or infected cells.
It does this using proteins on its surface,
which can bind to proteins on the surface
of these imposters. Each T cell is highly
specific – there are trillions of possible
versions of these surface proteins, which
can each recognise a different target.
Because T cells can hang around in the
blood for years after an infection, they also
contribute to the immune system’s “longterm
memory” and allow it to mount a
faster and more effective response when
it’s exposed to an old foe.
Several studies have shown that people
infected with Covid-19 tend to have T
cells that can target the virus, regardless
of whether they have experienced
symptoms. So far, so normal. But scientists
have also recently discovered that some
people can test negative for antibodies
against Covid-19 and positive for T cells
T cells are
a kind of
immune cell,
whose main
purpose is to
identify and
kill invading
pathogens
or infected
cells. It does
this using
proteins on its
surface, which
can bind to
proteins on
the surface
of these
imposters.
Each T cell is
highly specific
– there are
trillions of
possible
versions of
these surface
proteins,
which
can each
recognise
a different
target.”
that can identify the virus. This has led to
suspicions that some level of immunity
against the disease might be twice as
common as was previously thought.
Most bizarrely of all, when researchers
tested blood samples taken years before the
pandemic started, they found T cells which
were specifically tailored to detect proteins
on the surface of Covid-19. This suggests
that some people already had a pre-existing
degree of resistance against the virus before
it ever infected a human. And it appears to be
surprisingly prevalent: 40-60% of unexposed
individuals had these cells.
It looks increasingly like T cells might be
a secret source of immunity to Covid-19.
The central role of T cells could also help
to explain some of the quirks that have so far
eluded understanding – from the dramatic
escalation in risk that people face from the
virus as they get older, to the mysterious
discovery that it can destroy the spleen.
How immunity unfolds
Most people probably haven’t thought about
T cells, or T lymphocytes as they are also
known, since school, but to see just how
crucial they are for immunity, we can look
to late-stage Aids. The persistent fevers. The
sores. The fatigue. The weight loss. The rare
cancers. The normally harmless microbes,
such as the fungus Candida albicans – usually
found on the skin – which start to take over
the body.
During a normal immune response – to,
let’s say, a flu virus – the first line of defence
is the innate immune system, which
involves white blood cells and chemical
signals that raise the alarm. This initiates
the production of antibodies, which kick in a
few weeks later.
“And in parallel with that, starting out
about four or five days after infection, you
begin to see T cells getting activated, and
indications they are specifically recognising
cells infected with the virus,” says Hayday.
These unlucky cells are then dispatched
quickly and brutally – either directly by
the T cells themselves, or by other parts of
the immune system they recruit to do the
unpleasant task for them – before the virus
has a chance to turn them into factories that
churn out more copies of itself.
The good and bad news
So, what do we know about T cells and
Covid-19?
“Looking at Covid-19 patients – but also
I’m happy to say, looking at individuals
who have been infected but did not need
hospitalisation – it’s absolutely clear that
there are T cell responses,” says Hayday.
“And almost certainly this is very good news
for those who are interested in vaccines,
because clearly we’re capable of making
antibodies and making T cells that see the
virus. That’s all good.”
There is a catch, however. In many
patients who are hospitalised with more
serious Covid-19, the T cell response hasn’t
quite gone to plan.
“Vast numbers of T cells are being
affected,” says Hayday. “And what is
happening to them is a bit like a wedding
party or a stag night gone wrong – I
mean massive amounts of activity and
proliferation, but the cells are also just
disappearing from the blood.”
Disconcertingly, spleen necrosis is a
hallmark of T cell disease, in which the
immune cells themselves are attacked. “If
you look in post-mortems of Aids patients,
you see these same problems,” says Hayday.
“But HIV is a virus that directly infects T
cells, it knocks on the door and it gets in.” In
contrast, there is currently no evidence that
the Covid-19 virus is able to do this.
“There are potentially many explanations
for this, but to my knowledge, nobody has
one yet,” says Hayday. “We have no idea
what is happening. There’s every evidence
that the T cells can protect you, probably for
many years. But when people get ill, the rug
seems to be being pulled from under them
in their attempts to set up that protective
defence mechanism.”
Dwindling T cells might also be to blame
for why the elderly are much more severely
affected by Covid-19.
Hayday points to an experiment
conducted in 2011, which involved exposing
mice to a version of the virus that causes
Sars. Previous research had shown that
the virus – which is also a coronavirus and
a close relative of Covid-19 – triggered the
production of T cells,
What does this mean for long-term
immunity?
The fact that coronaviruses can lead to
lasting T cells is what recently inspired
scientists to check old blood samples taken
from people between 2015 and 2018, to see if
they would contain any that can recognise
Covid-19. The fact that this was indeed
the case has led to suggestions that their
immune systems learnt to recognise it after
being encountering cold viruses with the
similar surface proteins in the past.
Will this lead to a vaccine?
If old exposures to cold viruses really are
leading to milder cases of Covid-19, however,
this bodes well for the development of a
vaccine – since it’s proof that lingering T
cells can provide significant protection, even
years after they were made.
But even if this isn’t what’s happening,
the involvement of T cells could still be
beneficial – and the more we understand
what’s going on, the better.
“There really is an enormous spectrum
of vaccine design,” says Hayday. He’s
particularly encouraged by the fact that
the virus is evidently highly visible to the
immune system, even in those who are
severely affected.”
It seems likely that we are going to be
hearing a lot more about T cells in the future.
— The Health