Two molecules on the surfaces of T-cells a type of immune cell must work in tandem to help the T-cells cross from the bloodstream into infected tissues, where the T-cells initiate an immune or inflammatory response, researchers at UT Southwestern have discovered.

The research, which was done in mice, appears in the April 21 issue of the journal Immunity.

In order to fight certain infections, T-cells must migrate from the bloodstream and into infected tissue. T-cells also cross blood vessel walls to initiate inflammatory or autoimmune responses in diseases such as rheumatoid arthritis, type 1 diabetes, lupus, asthma, Crohn's disease and colitis.

Scientists know that two specific molecules, or receptors, on passing T-cells in the bloodstream interact with receptors on the walls of blood vessels. One T-cell receptor, called CD44, is responsible for getting the T-cells to "roll" along the blood vessel wall.

"CD44 governs the rolling behavior of the T-cell, where it touches and then lifts off the vascular wall," said Dr. Mark Siegelman, associate professor of pathology at UT Southwestern and senior author of the study.

A second receptor, VLA-4, stops the T-cells from rolling. This step in the process is called firm adhesion.

"You need both of these steps in order to get the T-cells out of the blood vessel and into tissue," Dr. Siegelman said. "Only by completing the second step, firm adhesion, has the T-cell committed to sticking and getting out."

In the new research, UT Southwestern scientists found that in order to get the T-cells to stick firmly to the vascular wall, the CD44 and VLA-4 receptors on the T-cell had to be physically linked. If they
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Contact: Amanda Siegfried
Amanda.siegfried@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
20-Apr-2004