杏吧原创

TREATMENT that might enable people to live with transplanted tissue without
having to take immunosuppressive drugs for the rest of their lives has edged a
step closer.

After being given an antibody and the immunosuppressive drug cyclosporin A
for just two weeks, mice accepted a transplant without short-term 鈥渁cute鈥�
rejection. More importantly, the organs did not suffer long-term 鈥渃hronic鈥�
rejection, the relentless attrition experienced by a foreign organ once it has
survived the initial onslaught.

At the moment, the only way for transplant patients to avoid chronic
rejection is to keep taking immunosuppressive drugs. But this makes them
vulnerable to infection and doesn鈥檛 always work. Some transplants still wither
away as their blood vessels thicken in response to the immune attack. But if the
new approach also works in humans, a short treatment could prevent both acute
and chronic rejection.

Rejection begins when B cells, dendritic cells and other 鈥渁ntigen-presenting
cells鈥� of the immune system pick up marker proteins from the foreign cells and
display them to killer T cells. This results in the proliferation of T cells
programmed to destroy any cells bearing the marker proteins.

This can only happen if the antigen-presenting cells bind to and activate
certain receptors on the surface of T cells. What Wayne Hancock and his
colleagues at Millennium Pharmaceuticals in Cambridge, Massachusetts, have
discovered is that a receptor on T cells called inducible co-stimulator, or
ICOS, seems to play a key role.

By giving mice antibodies that block ICOS and prevent T cells interacting
properly with B cells, the researchers stopped the T cells attacking foreign
tissue. Crucially, the transplants appear to be protected for good.

Earlier research has shown it鈥檚 possible to prevent acute rejection by
blocking other receptors on T cells, called CD28 and CD40, which also interact
with B cells. But this doesn鈥檛 prevent long-term rejection.

But researchers in the field are urging caution about the latest results. 鈥淚
don鈥檛 believe they鈥檝e shown it鈥檚 a magic bullet,鈥� says Jeffrey Bluestone, an
immunologist at the University of California in San Francisco. 鈥淚t doesn鈥檛 mean
we鈥檝e solved graft rejection, because ICOS is just another player we have to
consider,鈥� he says. 鈥淵ou should appreciate that there鈥檝e been 100 papers in the
literature like this over the past 10 years.鈥�

Bluestone says the findings would have been more convincing if Hancock and
his colleagues had given the animals a second transplant with tissue identical
to the first. If the mice had accepted that without any trace of rejection, it
would prove that the initial graft was fully tolerated.

He also believes that ICOS is simply one of the many 鈥渟witches鈥� on T cells
which gradually amplify the readiness of the T cells to attack. When all these
signals pass a certain threshold, the T cells multiply and attack the graft.
Bluestone speculates that a variety of antibodies that bind to these switches
will be needed to prevent the T cells attacking. 鈥淭he best treatment may be a
combination,鈥� he says.