BioEd Online

Despite being surrounded by a supposedly unbreachable defensive line, the body's central nervous system can still be attacked by autoimmune diseases such as multiple sclerosis.

Now, researchers led by Alexander Flügel, director of the Institute for Multiple Sclerosis Research at the University Medical Centre in Göttingen, Germany, have watched in real time as T cells — blood cells linked to the immune response — penetrate the central nervous system of rats and manifest as a disease.

"There's a question about how immune cells that attack the brain get entry because [it] is shielded by the blood-brain barrier," Flügel says. Histological studies have clearly shown immune cells can enter brain tissue, but no one has seen this happen until now. "Our question was, can we visualize this process?" he says.

To answer this question Flügel's team labelled some disease-causing T cells with green fluorescent protein and introduced them into the veins of rats. Then, using infrared lasers in a technique called two-photon imaging, they watched the movements of the cells as they caused experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. The work is reported in Nature¹.

Only recently has the technology needed for all these elements become sophisticated enough to make this work possible, says Flügel.

Unexpectedly, the researchers found that some assumptions about how T cells gain entry to the nervous system are misplaced. Textbook knowledge, says Flügel, is that the cells roll along blood vessels then attach and migrate into the nervous-system tissue.

Instead, as illustrated in the linked videos, his team found that after rolling along the the inside of the vessel, the cells stop then crawl back against the flow of blood before exiting the vessel. Also, once they have passed through the vessel they do not immediately infiltrate the nervous-system tissue. Rather, they continue to crawl along the outside of the vessels until they meet another type of blood cell, called phagocytes. Only then do they enter the nervous system and begin to manifest the disease.

The findings both improve researchers' understanding of how some treatments work and identify which structures involved in the movement of the T cells might be useful to target with future therapies.