Discovery of protein may lead to new immune-system therapy

Published: Thursday, February 29, 1996

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 webmaster@db.asucla.ucla.edu