Intravital real-time analysis of T-cell activation in health and disease

Antigenic activation is a central process in T-cell biology essential for efficient protection of the host from infections and tumors by the adaptive immune system. Furthermore, this process is of paramount importance for the initiation of autoimmunity. Many insights into the mechanisms of T-cell activation have been gained from real-time studies. The development of 2-photon microscopy transferred the focus of T cell activation to in vivo research and the analysis of the highly dynamic and complex T-cell response in the physiologic context of an animal model. In the last 15 years, real-time analysis of T-cell activation has progressed from a descriptive characterization of T-cell locomotion and visualization of T-cell contacts with putative antigen-presenting cells in ex vivo explants toward true intravital imaging using more functionally informative indicators of TCR-driven signaling to spot and quantify productive T-cell-APC interactions in situ. In this review we will briefly summarize and discuss current approaches to the real-time analysis of T-cell activation in vivo and their impact on our understanding of T cell function under homeostatic and pathological conditions.