our immune systems to win the battle against disease
and epidemics Ð once thought curable Ð are on the rampage
again, as medicines become increasingly ineffective against
drug-resistant strains of diseases such as TB and malaria.
But why aren't our own immune systems able to defend us
properly? Immunologist Professor Simon Carding believes
his research team may have found an important piece in
the puzzle of how our immune systems work, opening up
new ways to treat a whole range of diseases.
Delta T-cells (GDT-cells) (pictured
left) were discovered fifteen years ago,
but their function has remained a mystery Ð until now.
They are found in all mammals, and earlier research showed
they were often present in large numbers in patients suffering
from infectious or autoimmune diseases, such as TB, malaria,
listeriosis, rheumatoid arthritis, multiple sclerosis
and coeliac disease. Scientists believed they were part
of the problem, helping these diseases to progress, but
Professor Carding believes that the GDT-cells are actually
part of the cure.
of the Leeds research team's particular interest is in
tuberculosis, a disease which was virtually eradicated
from the UK, but is a major killer in the developing world,
with over two million deaths from the disease each year.
TB is very much determined by individual immune response:
seventy percent of those who come in contact with the
disease will eradicate the bacteria and show no signs
of infection. There are nevertheless over eight million
new cases of TB each year, many due to the AIDS epidemic,
as AIDS is one of the most common reasons for those exposed
or infected to develop the disease.
Carding (pictured above)
said: " Many of the symptoms shown by TB patients Ð such
as chronic inflammation Ð are not directly caused by the
TB bacteria, but rather by the immune system killing off
healthy cells in the body. As such, TB has a lot in common
with autoimmune diseases where the off switch for the
immune system is missing or defective resulting in chronic
all these diseases, the key to better treatment might
not be to directly attack the organism, but to find out
why the immune system is unable to respond properly to
the disease. We believe that the Gamma Delta T-cells may
provide an answer."
mice which are genetically deficient in these cells are
infected with a bacteria, they show chronic inflammation
and extensive tissue damage that results from the inability
to switch off the immune response once the invading bacteria
have been eliminated. To see if there is a correlation
in humans, Professor Carding and his team have been working
with clinicians treating large numbers of patients with
advanced TB in China, Turkey, Mexico, the USA, Canada
showed that patients start with normal levels of the cells,
but lose them as the disease progresses. Patients who
respond well to chemotherapy treatment see their GDT-cells
return to a normal level. We believe if we can rearm the
cells, then patients may be able to fight not only TB,
but a whole range of diseases, more effectively."
research team has found that the GDT-cells role is to
kill off other cells called macrophages, the most important
cells in the immune system. Macrophages perform various
beneficial functions, such as destroying tumour cells,
killing pathogenic microorganisms, and activating the
they can also be harmful, producing toxic substances which
damage or destroy healthy cells. Professor Carding's research
team have shown that GDT-cells regulate the levels of
macrophages by eliminating them once their job has been
done, ensuring a balanced immune response.
the battle some members of Carding's research team:
Charlotte Egan and Sheena Cruickshank (above left to right)
and Sam Broad (below)
scientists believe that the macrophages express a substance
Ð or antigen Ð to which the Gamma Delta T-cells react.
If the wrong messages go out, or if the GDT-cells fail
to react, the immune response continues unregulated, causing
tissue damage and chronic inflammation.
Carding said: "If we can discover what triggers the GDT-cells,
it will open the way to new treatments for auto-immune
and infectious diseases. If the cells are still present,
we could reactivate them. It will be harder to regenerate
the GDT-cells if the disease actually kills them off,
but it is still potentially possible."
problem for the scientists is that the substance which
triggers the GDT-cells could be one of many proteins or
may not be a protein at all. Using a process of elimination,
and informed guesswork to target likely candidates, the
scientists are looking at certain molecules, extracted
from the surface of the macrophages. Separated into constituent
parts, these molecules are then tested against the GDT-cells
and any possible reaction monitored.
successful in finding this substance, the research could
open up new forms of treatment, using the immune system
itself to fight the disease and bypassing the problem
of antibiotic resistance.
Carding said: "Our current funding will run for around
three more years, and we hope to have identified the antigens
recognised by the GDT-cells by then. Forming treatments
based on the research will take much longer."
breakthrough has been well received by other research
groups around the world, and Professor Carding has been
presenting the findings at international meetings throughout
Europe and the USA.
full review of the research is to be published in Nature's
immunology review next year.