“T cells are particularly good at making transient contacts with other cells and then moving on,” says Davis. “It's a specialized function of T cells, natural killer cells, and similar cell types.” His group now shows that such short-lived greetings often leave in their wake membrane tethers known as nanotubes.
These delicate actin-filled tethers have been seen linking neuronal PC12 cells as well as macrophages, B cells, and other immune cell types. But the T cell nanotubes were distinct. Unlike the open-ended linkages of PC12 cells, these nanotubes maintained a membrane junction between T cells, either within the nanotube or at its tip. They also had the ability to curve around obstacles, as revealed when T cells were set in a 3D matrix.
The resolution of in vivo fluorescence microscopy is not yet sufficient to detect nanotubes directly. But circumstantial evidence suggests they exist in vivo, as cell surface proteins can be detected moving between cells somehow. Davis and colleagues are currently trying to identify immune cell materials that traffic within the tubes and the functional consequences of any transfer between T cells. Unlike myeloid cells, T cells were unable to transmit calcium signals via their nanotubes.
Whether nanotubes are used for T cell processes or are a simple byproduct of membrane physics, at least one virus has learned to exploit them. This opportunist is HIV, which invades and replicates within T cells. HIV antigens were found in nanotubes emanating from infected cells. And previously uninfected cells that connected to such nanotubes occasionally wound up with their own allotment of these antigens. Transfer required the viral receptor, CD4, suggesting that HIV transfer between cells by nanotubes requires membrane fusion mediated by HIV's Envelope protein.