Persistent immunotoxic effects of tributyltin in human natural killer cells can be reversed by interleukin 2

Tributyltin (TBT) is a widespread environmental contaminant due to its use in marine antifouling paints and as an anti-microbial agent in other applications. There are measurable levels of TBT in some samples of human blood. Natural killer (NK) cells are lymphocytes capable of killing tumor and virally infected cells. Previously, we have shown that a 1 h exposure to 300 nM TBT caused a permanent decrease in the ability of human NK cells to bind to and destroy tumor target cells and in their expression of certain functionally relevant cell surface markers. The present study investigates the effect of the NK-stimulatory cytokine, interleukin (IL) 2 on TBT-induced decreases in NK cytotoxicity, binding function, and expression of CD16 and CD56. A 1 h exposure to 300 nM TBT followed by 24 h in TBT-free media decreased cytotoxic function by 80%, and expression of CD16 by 16%. When 10 ng/mL IL-2 was present during the 24 h incubation there was no statistically significant decrease in cytotoxicity or expression of CD16. A 96 h incubation in TBT-free media produced decreases in cytotoxicity (99%), binding function (65%), and expression of CD16 (48%) and CD56 (51%). IL-2 was able to reverse the TBT-induced decreases in each of these parameters seen after 96 h. These results suggest that IL-2 restoration of NK ability to bind target cells correlates with its ability to restore CD16 and CD56 expression. Additionally, neither the loss of cytotoxic function (seen in the 24 or 48 h periods following TBT exposure) nor its restoration by IL-2 can be substantially explained by the effects of TBT exposure on CD16 and CD56 expression or target binding.