Immunological giants and dwarves
Munich scientists study single immune cells as they defend against a disease
Munich, 14 March 2013. The human body is under constant attack from a multitude of different pathogens. Considering the frequency of these attacks from viruses and bacteria, we actually get sick extremely rarely. This is thanks mostly to an elite team of immune cells, called the killer T cells: When we need an immune response, these killer cells multiply in two ways to combat the pathogens quickly and lastingly, thus preventing the onset of disease. Researchers from the Institute for Medical Microbiology, Immunology and Hygiene (MIH) of Technische Universität München and cooperative partners at the German Cancer Research Centre (DKFZ) Heidelberg have now explained in detail how this multiplication process takes place. They have observed the process starting from single immune cells. From their findings, the researchers hope to find indications of how we can help people with compromised immune systems fight diseases or tumours. The results obtained under the umbrella of the German Centre for Infection Research (DZIF) are being published today in the prestigious journal Science (DOI: 10.1126/science.1235454).
“Until now, it has only been possible to observe groups of immune cells as they combat pathogens,” Prof. Dr. med. Dirk Busch, Director of MIH says. “We have enhanced the methods such that we can now observe single T cells.” To do this, the researchers injected specially marked T cells into mice in which they then triggered a specific immune response. After about eight days, Busch and his team analysed how many and what types of offspring these individual cells produced. Veit Buchholz, physician and research scientist at MIH and first author of the Science paper explains: “The offspring of a parent killer T cell embark upon different careers. Some multiply rapidly and create a huge number of descendants. These we call ‘giants’. They immediately start attacking the pathogens, quickly and effectively defeating them. Yet these giants are only very short lived. A different kind of offspring from the T cells – the ‘dwarves’ – reproduce slowly, but live much longer. Their few descendants offer long-term protection: they form the immunological memory of the pathogen.”Which way a given cell will develop, the scientists cannot predict. This happens randomly, Buchholz says. “First, a set of about 50 starting cells generate an immune response, the extent and composition of which are entirely predictable using mathematical models.” Using biomathematical modelling methods developed in close collaboration with the research group of Prof. Dr. Thomas Höfer at DKFZ, the researchers have discovered that the starting ratio of giants to dwarves may be of great long-term significance to the immune system. If there are more rapidly multiplying cells than slowly multiplying cells, then the immunological memory is worse; when the same pathogen comes along again, there is no adequate immune response. “It could be therapeutically beneficial in immunocompromised people – such as the elderly or cancer patients – to nudge the ratio in favour of the dwarves at the beginning of an immune response,” Prof. Dirk Busch says. “Then the response would not be so much a flash in the pan, but rather a longer and more effective immune defence.”
