How do immune cells fine-tune their response to threats? This review examines the intricate calcium signaling mechanisms in T lymphocytes, highlighting the remarkable variety of Ca2+ signals generated by the interactions of multiple Ca2+ sources and sinks within the cell. The review provides a comprehensive overview of how these signals trigger T-cell activation and influence downstream events. Following engagement of the T cell receptor, intracellular channels release Ca2+ from intracellular stores, triggering prolonged Ca2+ influx through store-operated Ca2+ (CRAC) channels in the plasma membrane. The amplitude and dynamics of the Ca2+ signal are shaped by K+ channels, membrane potential, and mitochondria. Ca2+ signals guide lymphocytes to choose between alternate fates in response to antigenic stimulation, helping stabilize contacts between T cells and antigen-presenting cells through changes in motility and cytoskeletal reorganization. Over minutes to hours, the amplitude, duration, and kinetic signature of Ca2+ signals increase the efficiency and specificity of gene activation events. This complexity of the signals contains a wealth of information that may help instruct lymphocytes.
Published in the Annual Review of Immunology, this review aligns perfectly with the journal's dedication to providing authoritative syntheses of key topics in immunology. By examining calcium signaling mechanisms in T lymphocytes, the paper addresses a fundamental aspect of immune cell activation and function, a central theme for the journal's readership.