Understanding how HTLV causes disease
White Blood Cells Crossing the Blood-brain Barrier: A Gateway to Disease
It is not known why some people develop
HAM/TSP whereas most people infected with
HTLV-1 remain disease-free. However, it is widely supposed that HAM/TSP is initiated by the infected white blood cells travelling out of the blood and into the central nervous system. There is a barrier which protects the central nervous system and this is known as the blood-brain barrier, as the main organ of the nervous system is the brain. This barrier includes a layer of cells called endothelial cells. Researchers in the Department of Immunology at Imperial College (St Mary's Campus), have been studying the movement of the white blood cells, called T cells, across the endothelial cells.
Endothelial cells can be grown in the laboratory to form a layer. They were grown on plastic which had small holes all over it. The endothelial cells were bigger than the holes, so did not fall through, but white blood cells are small enough to pass through. The white blood cells from HTLV-1-infected patients and from uninfected people were put on this endothelial cell layer on top of the plastic. Any T cells that travelled through the endothelial cell barrier were collected and counted. When the endothelial cells were not there, and the T cells just had to pass through the holes in the plastic, all the cells passed through at the same speed.
The studies showed that uninfected cells and cells infected with HTLV-1 both travelled across the barrier at the same rate. However, if the infected T cells had a virus protein on their surface called "Tax", they were more likely to pass through the barrier.
There are different proteins on the endothelial cells and it is possible that these interact with the proteins on the HTLV-1-infected cells that have the Tax protein on their surface. This Tax protein is known to cause the T cells to produce lots of different proteins and these proteins could be helping the T cell to push its way between the endothelial cells. The researchers now wish to discover which proteins are involved, with the aim to find ways to block this migration of infected cells which cause disease.