To address these questions, researchers at TUM began by introducing specially marked T cells into mice and then triggering a specific immune reaction. Around seven days later, they were able to determine how many descendant cells, and what kinds, had been generated by individual T cells. Biomathematical modeling, using an approach co-developed with the group of Prof. Thomas Hoefer at Heidelberg, helped to explain what the data showed. "One can't predict which 'career paths' the descendants of an individual killer T cell will take, " says first author Veit Buchholz, a medical resident at TUM. "This is a matter of chance, like a single roll of the dice. To generate a predictable immune response, we have found that a sample of at least 50 individual cells is needed."
From analysis of many of the huge populations of short-lived killer cells and the relatively tiny populations of long-lived memory cells, the researchers were able to reconstruct the T cells' development program and predict their behavior: All of the cells proceed along the same path of development, but they don't go the same distance. That is, the few cells that generate giant populations of short-lived infection fighters have gone through the same stage as those fated to produce memory cells but they have left that stage behind to provide immediate protection.
Beyond the results themselves, another important outcome of this study is increased confidence in the combined power of the in vivo and in silico approaches. "The fact that the experimental results confirmed our predictions in detail has strongly supported our theory," says Prof. Hoefer, leader of the Heidelberg group.
|Contact: Patrick Regan|
Technische Universitaet Muenchen