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