"We have shown that long tubes made of cell membrane readily form between immune cells and a variety of other cell types," team leader Daniel Davis of Imperial College London, told nanotechweb.org. "These membrane nanotubes could constitute a new way for cells to communicate with each other. However, the downside is that viruses might use these connections to efficiently spread between cells."
The existence of such membrane nanotubes between T-type immune cells was unknown until now. Using light microscopy, Davis and colleagues found that when these cells make contact and then move part, they frequently remain connected by tubular membranes. These tubes are about 100–300 nm across and can be up to eight cell diameters long. The rate at which the nanotubes form and their lifetime depends on how long the T-cells remain in contact with each other and how fast they subsequently separate, explains Davis.
By using fluorescence and electron microscopy, the researchers also saw that the T-cell nanotubes were not open-ended. Instead, they connected cells together via junctions within the tubes. These junctions allow the cells to communicate with each other by signal transfer.
Novel mechanism of HIV transmission?
Live cell microscopy on infectious fluorescent-tagged HIV-1 showed the virus travelling along the nanotubes, from infected to uninfected cells. "The membrane nanotubes thus represent novel physical connections between T-cells that can be exploited by HIV for efficient cell-to-cell spread," stated Davis. This new mechanism of HIV transmission could potentially open up new avenues for drug targets, he added.
According to the team, communication via such direct connections between cells would be much more efficient than communication via ordinary soluble secretions, but more work is still needed to test this hypothesis.
"Whether or not viruses may exploit membrane nanotubes to move between cells has not yet been tested," Davis stressed. "Since the ability of HIV-1 to spread between cells is an important mark of its virulence, this novel mechanism of HIV transmission may indeed be important to its pathogenicity."
First time in T-cells
Although researchers have already seen similar links forming between other kinds of cells, including brain cells and certain types of immune cell, this is the first time that they have been observed in T-cells. Similar links are created when cells divide to produce new cells, but the new membrane nanotubes are unique because they have distinct junctions, or breaks, where the membrane material from each of the two cells meets.
The team now plans to discover how the membrane nanotubes actually form. It would also like to test for the membrane nanotubes in vivo.
The results were reported in Nature Cell Biology.