Cadmium-induced apoptosis and phenotypic changes in mouse thymocytes

At present cadmium (Cd)-induced immunotoxicity and the mechanisms involved have not been fully elucidated. The main objective of the present study is to explore the apoptogenic property of Cd in primary cultured mouse thymocytes and its effect on cell surface marker expression and phenotypic changes. Cd-induced thymocyte apoptosis was determined by TdT-mediated dUTP nick end labeling (TUNEL) assay, DNA content/cell cycle analysis and DNA gel electrophoresis. The results showed that Cd was able to cause apoptosis in mouse thymocytes in a time- and dose-dependent manner. Moreover, different subsets of thymocytes possessed different susceptibility to the apoptotic effect of Cd, in the order of CD8(+) > CD4(-)CD8(-) (double negative cells, DN) > CD4(+)CD8(+) (double positive cells, DP) > CD4(+). Cd treatment also altered thymocyte surface marker expression, leading to evident phenotypic changes. Such changes were characterized by a decline in DP cells and a marked decrease in CD4(+)/CD8(+) ratio, mainly due to a significant increase in CD8(+) subsets. These observations help to obtain a better understanding of the immunotoxic and immunomodulatory effects of Cd.