License for Self-destruction

Photo: Lung explant

The autoaggressive T cells (green)
accumulating in the lung. They
accumulate in specialized lymphatic
structures (yellow arrow);
© University Göttingen

Specialized immune cells, so-called T cells, are held to be the cause of MS. Even though nearly every healthy human harbors potentially disease-causing T cells in his or her immune system, only around 0.1 percent of the population actually develops a manifest MS. One of the reasons for this is that normally T cells are stopped from entering the brain by a virtually impermeable vascular barrier separating the central nervous system from the blood circulation. “Earlier work in experimental MS research showed that when T cells are pre-activated outside nervous tissue they are very well able to pass into the brain and trigger MS-like symptoms there”, explains Professor Alexander Flügel. “However, we wanted to find out exactly where in the body these T cells are activated and exactly which properties enable them to overcome the blood–brain barrier.”

The scientists initially discovered that disease-causing T cells cannot enter the brain immediately after activation but rather have to “learn” how to do so. During this learning process the T cells completely re-gear themselves. They stop dividing and throttle their production of proteins that foment inflammation. Instead they are programmed for migration: they become more motile, and specialized receptors appear on their surface membranes. These receptors are like little antennae that enable a T cell to orientate itself by picking up signals from its environment and to cleave to surfaces.

The scientists discovered that the receptor Ninjurin 1, previously unknown to have any relevance to T cells, controls the ability of T cells to cleave to the inner side of the brain’s blood vessels and thus is of great significance for the migration of T cells from the blood into the nervous tissue. Once the T cells arrive in the nervous tissue, this program goes into reverse: the immigrant T cells are reactivated and they produce inflammatory mediators that set the tissue-damaging autoimmune processes in motion typical to MS.; Source: University Medical Center Göttingen