How Our Liver Kills 'Killer Cells'

[Guest guest]

http://www.sciencedaily.com/releases/2011/09/110919151324.htm

How Our Liver Kills 'Killer Cells'

ScienceDaily (Sep. 22, 2011) — Our livers can fight back against the immune

system -- reducing organ rejection but also making us more susceptible to liver

disease. Scientists at the Centenary Institute in Sydney have seen for the first

time (in mice) how the liver goes independent, engulfing and destroying the

body's defence troops -- T-cells.

Their discovery, published overnight in PNAS (Proceedings of the National

Academy of Sciences), opens the way to both new approaches to transplant

rejection, and to the fight against hepatitis and other chronic liver diseases

which affect over 200,000 Australians and hundreds of millions of people

worldwide.

" In 2004, we discovered that healthy liver cells can engulf active immune cells,

known as T-cells -- and now we've seen that those T-cells are actually

destroyed, " says Dr Bertolino, the leader of the research team at the

Centenary Institute.

" The liver is an amazing organ, " Dr Bertolino says. " Most people think it just

breaks down alcohol, but it's the factory of the body -- breaking down

substances we don't want and making the ones that we do.

" We now know liver cells also have the ability to subvert the orders of the

immune system, " he says, " Our discovery might explain why liver transplants have

lower rejection rates than other organ transplants. "

" When first told me he had evidence T-cells might be eaten by liver

cells, showing a possible link to the liver's ability to dial down the immune

response, I thought the idea was crazy, " says lead author Volker Benseler. But

Volker accepted 's challenge to prove it and went on to find healthy

mouse liver cells eating T-cells, which was unexpected as this 'cell

cannibalism' had only previously been seen in tumour cells.

One potential benefit of the research is reducing rejection in organ

transplants. About 200 liver transplants are performed in Australia each year

and up to 25 per cent of cases end in rejection.

In transplantation, the new organ is seen by the body as a foreign object: the

spleen or lymph nodes tell naïve T-cells to replicate and turn into killer

T-cells, which are sent off to invade and kill the 'foreign' cells.

What the researchers have discovered is the liver goes around this process:

liver cells signal to naïve T-cells and digest them before they have a chance to

become killer T-cells.

Centenary Institute's Liver Unit leader, Professor Geoff McCaughan, says the

cocktail of immunosuppressive drugs that organ transplant patients receive

reduce the odds of organ rejection but makes patients' immune systems weak,

leaving them open to serious infection from otherwise minor illnesses like cold

or flu. These drugs also predispose the patient to long-term heart disease and

cancer. " If we can harness the way the liver controls T-cells, then long-term

there is a chance that transplant patients won't need these drugs, " he says.

Another spin-off of this latest work could be to find a way to dial down the

liver's destruction of T-cells, increasing the liver's defence against

infections like hepatitis.

In Australia, 217,000 people are living with chronic hepatitis C and it is

estimated that 170 million people worldwide are infected with hepatitis C, for

which there is no vaccine.

Exploiting signalling pathways between the liver and the T-cells is one possible

outcome of this discovery, but first the molecular biology that underpins those

pathways will need to be worked out.

" It could be another ten years plus before we see drugs derived from this work

enter clinical trials, " Dr Bertolino says.

However, the research opens up a new question -- why? " We don't yet know why the

liver has developed this ability, " says Dr Bertolino. " The discovery reminds us

that we still have a lot to learn about the liver. "

The work was conducted at the Centenary Institute and at Sydney's Concord RG

Hospital, at the ANZAC Research Institute and CERA. Dr Benseler is now

completing surgical training in Germany.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff)

from materials provided by Centenary Institute.

--------------------------------------------------------------------------------

Journal Reference:

1.Volker Benseler, Alessandra Warren, Vo, E. Holz, Szun S. Tay,

G. Le Couteur, Eamon Breen, C. , Nico Van Rooijen,

Mcguffog, Hans J. Schlitt, G. Bowen, Geoffrey W. Mccaughan,

Bertolino. Hepatocyte entry leads to degradation of autoreactive CD8 T cells.

Proceedings of the National Academy of Sciences, 2011; DOI:

10.1073/pnas.1112251108

[Guest guest]

http://www.sciencedaily.com/releases/2011/09/110919151324.htm

How Our Liver Kills 'Killer Cells'

ScienceDaily (Sep. 22, 2011) — Our livers can fight back against the immune

system -- reducing organ rejection but also making us more susceptible to liver

disease. Scientists at the Centenary Institute in Sydney have seen for the first

time (in mice) how the liver goes independent, engulfing and destroying the

body's defence troops -- T-cells.

Their discovery, published overnight in PNAS (Proceedings of the National

Academy of Sciences), opens the way to both new approaches to transplant

rejection, and to the fight against hepatitis and other chronic liver diseases

which affect over 200,000 Australians and hundreds of millions of people

worldwide.

" In 2004, we discovered that healthy liver cells can engulf active immune cells,

known as T-cells -- and now we've seen that those T-cells are actually

destroyed, " says Dr Bertolino, the leader of the research team at the

Centenary Institute.

" The liver is an amazing organ, " Dr Bertolino says. " Most people think it just

breaks down alcohol, but it's the factory of the body -- breaking down

substances we don't want and making the ones that we do.

" We now know liver cells also have the ability to subvert the orders of the

immune system, " he says, " Our discovery might explain why liver transplants have

lower rejection rates than other organ transplants. "

" When first told me he had evidence T-cells might be eaten by liver

cells, showing a possible link to the liver's ability to dial down the immune

response, I thought the idea was crazy, " says lead author Volker Benseler. But

Volker accepted 's challenge to prove it and went on to find healthy

mouse liver cells eating T-cells, which was unexpected as this 'cell

cannibalism' had only previously been seen in tumour cells.

One potential benefit of the research is reducing rejection in organ

transplants. About 200 liver transplants are performed in Australia each year

and up to 25 per cent of cases end in rejection.

In transplantation, the new organ is seen by the body as a foreign object: the

spleen or lymph nodes tell naïve T-cells to replicate and turn into killer

T-cells, which are sent off to invade and kill the 'foreign' cells.

What the researchers have discovered is the liver goes around this process:

liver cells signal to naïve T-cells and digest them before they have a chance to

become killer T-cells.

Centenary Institute's Liver Unit leader, Professor Geoff McCaughan, says the

cocktail of immunosuppressive drugs that organ transplant patients receive

reduce the odds of organ rejection but makes patients' immune systems weak,

leaving them open to serious infection from otherwise minor illnesses like cold

or flu. These drugs also predispose the patient to long-term heart disease and

cancer. " If we can harness the way the liver controls T-cells, then long-term

there is a chance that transplant patients won't need these drugs, " he says.

Another spin-off of this latest work could be to find a way to dial down the

liver's destruction of T-cells, increasing the liver's defence against

infections like hepatitis.

In Australia, 217,000 people are living with chronic hepatitis C and it is

estimated that 170 million people worldwide are infected with hepatitis C, for

which there is no vaccine.

Exploiting signalling pathways between the liver and the T-cells is one possible

outcome of this discovery, but first the molecular biology that underpins those

pathways will need to be worked out.

" It could be another ten years plus before we see drugs derived from this work

enter clinical trials, " Dr Bertolino says.

However, the research opens up a new question -- why? " We don't yet know why the

liver has developed this ability, " says Dr Bertolino. " The discovery reminds us

that we still have a lot to learn about the liver. "

The work was conducted at the Centenary Institute and at Sydney's Concord RG

Hospital, at the ANZAC Research Institute and CERA. Dr Benseler is now

completing surgical training in Germany.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff)

from materials provided by Centenary Institute.

--------------------------------------------------------------------------------

Journal Reference:

1.Volker Benseler, Alessandra Warren, Vo, E. Holz, Szun S. Tay,

G. Le Couteur, Eamon Breen, C. , Nico Van Rooijen,

Mcguffog, Hans J. Schlitt, G. Bowen, Geoffrey W. Mccaughan,

Bertolino. Hepatocyte entry leads to degradation of autoreactive CD8 T cells.

Proceedings of the National Academy of Sciences, 2011; DOI:

10.1073/pnas.1112251108