Assessing T lymphocyte function and differentiation by genetically encoded reporter systems

• Various aspects of T cell function and fate can be studied with genetic reporters.
• Genetic reporters can elucidate functions with minimal perturbation of biological systems.
• Synthetic biology approaches allow novel reporter setups.
• Pros and cons of different setups must be considered when designing reporter systems.

Upon infection, antigen-specific T lymphocytes become activated, proliferate, differentiate, and acquire various effector functions. Much of our understanding of the molecular mechanisms underlying these processes derives from studies leveraging gene deletion, RNAi, and overexpression approaches. However, these perturbations do not inform on the regulation of gene activity under physiological conditions. Genetic reporter systems that couple biological events to detectable output signals are capable of providing this information. Here, we review the reporter approaches being currently used to investigate various aspects of T cell behavior, and discuss advantages and disadvantages inherent to different designs. We outline emerging applications based on recent advances in other fields, and highlight the potential of synthetic biology and genome engineering to address open questions in the field.