Calcium signal dynamics in T lymphocytes: Comparing in vivo and in vitro measurements

Amplitude and kinetics of intracellular Ca²⁺ signals ([Ca²⁺]_int) determine many immune cell functions. To mimic in vivo changes of [Ca²⁺]_int in human immune cells, two approaches may be best suited: 1) Analyze primary human immune cells taken from blood under conditions resembling best physiological or pathophysiological conditions. 2.) Analyze the immune system in vivo or ex vivo in explanted tissue from small vertebrate animals, such as mice. With the help of genetically encoded Ca²⁺ indicators and intravital microscopy, [Ca²⁺]_int have been investigated in murine T lymphocytes (T cells) in vivo during the last five years and in explanted lymph node (LN) during the last 10 years. There are several important reasons to compare [Ca²⁺]_int measured in primary murine T lymphocytes in vivo and in vitro with [Ca²⁺]_int measured in primary human T lymphocytes in vitro. First, how do human and murine data compare? Second, how do in vivo and in vitro data compare? Third, can in vitro data predict in vivo data? The last point is particularly important considering the many technical challenges that limit in vivo measurements and to reduce the number of animals sacrificed. This review summarizes and compares the results of the available publications on in vivo and in vitro [Ca²⁺]_int measurements in T lymphocytes stimulated focally by antigen-presenting cells (APC) after forming an immunological synapse.