A calcium optimum for cytotoxic T lymphocyte and natural killer cell cytotoxicity

Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are required for host defense. They destroy malignant target cells like cancer cells. Among metal cations, Ca²⁺ plays a prescinded role for CTL and NK cytotoxicity as it is the only cation used as ubiquitous second messenger. Measuring intracellular Ca²⁺ concentrations [Ca²⁺]_int in single cells has greatly changed our understanding of Ca²⁺ signaling. Yet, comparing the role of Ca²⁺ in the pre-[Ca²⁺]_int and [Ca²⁺]_int measurement era reveals that even in the pre-[Ca²⁺]_int measurement era (before 1980), the functions of Ca²⁺ and some other metal cations for the cytotoxic immune response were well established. It was even shown that Ca²⁺ influx across the plasma membrane but not Ca²⁺ release from intracellular sources is relevant for lymphocyte cytotoxicity and that very little Ca²⁺ is needed for efficient lymphocyte cytotoxicity against cancer cells. In the [Ca²⁺]_int measurement era after 1980, many of the important findings were better and more quantitatively refined and in addition the molecules important for Ca²⁺ transport were defined. The unexpected finding that there is a Ca²⁺ optimum of CTL and NK cell cytotoxicity deserves some attention and may be important for anti-cancer therapy.