Killer T-cells are effective against viruses only through teamwork
Killer T-cells must cooperate to effectively eliminate virus-infected cells
Cells of the immune system must work together closely to protect our body from pathogens. Various types of immune cells are facing bacteria and Viruses "eye-to-eye". And none do their jobs more precisely and elegantly than the cytotoxic T-Lymphocytes, which are killer T-cells that recognise and specifically kill virus-infected cells of the body. New vaccines and cell therapeutic agents are to utilise this mechanism - but much remains unknown about how this "James Bond of the immune system" works.
A team from the Institute of Immunology of the Hannover Medical School (MHH) directed by Prof Reinhold Förster und Dr Stephan Halle, as well as team members of Prof Martin Messerle from the MHH's Institute of Virology recently reported in "Immunity", a professional journal, on how effective killer T-cells are in killing virus-infected target cells. Using a method called 2-photon microscopy, the researchers successively viewed individual killer T-cells doing their work in virus-infected tissues using time-lapse video.
It was generally assumed that Killer T-cells were able to recognise new target cells in quick succession and to kill them by themselves. The MHH researchers now noted in several different infection models that killer T-cells are effective only if they work "as a team" of three or more killer T-cells attacking the same infected cell simultaneously or in quick succession. "Obviously, individual killer T-cells differ clearly in terms of their effectiveness and the target cell is damaged sufficiently only by means of a synchronised assault," says Förster. In their mathematical model-supported analysis, the MHH researchers collaborated closely with Prof Michael Meyer-Hermann and Alexey Uvarovskii from the System Immunology Department of the Helmholtz Centre for Infection Research (HZI) in Braunschweig.
"We also saw that killer T-cells usually do not enter into stable interactions with their target cells, but are in constant and very dynamic motion. This allows additional killer T-cells to reach a certain target cell," explains Halle.
These results shed a new light on how killer T-cells destroy their targets in the organism. Accordingly, future vaccination strategies should be optimised with a view to generating sufficient numbers of these highly mobile and cooperatively attacking killer T-cells.
Stephan Halle, Kirsten Anja Keyser, Felix Rolf Stahl, Andreas Busche, Anja Marquardt, Xiang Zheng, Melanie Galla, Vigo Heissmeyer, Katrin Heller, Jasmin Boelter, Karen Wagner, Yvonne Bischoff, Rieke Martens, Asolina Braun, Kathrin Werth, Alexey Uvarovskii, Harald Kempf, Michael Meyer-Hermann, Ramon Arens, Melanie Kremer, Gerd Sutter, Martin Messerle, Reinhold Förster. In Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity. Immunity. 2016 Feb 9. DOI: 10.1016/j.immuni.2016.01.010.