Discovery of protein may lead to new immune-system therapy

Discovery of protein may lead to new immune-system therapy

By Jennifer K. Morita

Daily Bruin Staff

A UCLA doctor in the department of pathology has discovered a
potential new method for controlling the body’s immune system
through a molecule that triggers T-cells to commit suicide.

T-cells are the body’s defense against foreign invaders such as
viruses and parasites, said UCLA pathologist Linda Baum. T-cells
also fight tumor cells. But after they respond to the invading
agent, the T-cells undergo a suicide pathway, Baum explained.

Baum and her team of researchers studied what triggered the
cells to "commit suicide," and found a protein called
galectin-1.

"Other molecules are known to trigger this suicide pathway but
those are made by the T-cells themselves," Baum said. "Ours were
made by the surrounding tissue, so it’s a homicide instead of a
suicide."

This homicide program, or apoptosis, could potentially be useful
for battling diseases by prolonging the T-cell’s ability to fight
the disease, by interrupting the galectin-1 process, according to
Baum.

Apoptosis could also be used to repress the immune system in
auto-immune diseases such as lupus and diabetes. In auto-immune
diseases, the cells recognize body tissues as foreign or as if the
tissues were a virus, Baum explained.

"The cells have lost the ability to discriminate normal from not
normal and T-cells begin attacking the body’s own tissues," Baum
said. "In these diseases, the suicide program has gone awry."

The trick is the way to control galectin-1," Baum said. "We want
to work on the basic mechanism and eventually find an application
to turn up or turn down the immune system."

Researchers are studying what galectin-1 binds to on the surface
of the T-cell when it undergoes apoptosis.

"We’re trying to determine what the counter receptors are on the
surface of the cell," said Karen Pace, a graduate student working
with Baum.

"On the surface of the cell, there are glyco-proteins, little
receptors sticking up from the surface of the cell," Pace said. "We
didn’t know which ones galectin-1 bound to, there are so many
candidates.

"Only a few counter receptors might bind to galectin-1 and are
able to transduce the signal that causes apoptosis," Pace said.

Baum and her researchers were able to identify two possible
counter receptors.

But although the discovery of galectin-1 shows the potential for
a new method of controlling the immune system, Baum emphasized
that, so far, her study has been conducted only in the
laboratory.

"This is pure test tube stuff," Baum said.

When galectin-1 was added to t-cells, researchers were able to
see the t-cells die under the microscope.

"Immediately, in the short term, this means nothing for
patients," said Nancy Perillo, a post-doctoral student working with
Baum. "It takes a long time for something like this to ultimately
change therapy procedures."

It’s interesting because several tumors have been found to
produce galectin-1, regulating the immune system and inhibiting the
immune response," Perillo said.

Julie Nguyen, a graduate student who has just started working
with Baum on her study, said the discovery is relevant in
immunology, particularly with auto-immune diseases.

"It plays a significant role and hopefully we can find something
to broaden our understanding," Nguyen said.

Perillo added that in animal models, galectin-1 inhibited
auto-immune diseases.

"But that’s in an animal model, and no one has understood why,"
Perillo said. "Our finding may shed light on this and maybe
important ultimately in cancer therapy … but that’s a long way
off."Comments to [email protected]