The value of in vitro immune function tests in the detection of potential immunotoxicants

Groups of rats were treated with different doses of cyclosporin A for 28 days. Their spleens were then removed aseptically and used to prepare single cell suspensions. These were examined for their proliferative response to the T-cell mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A), and the B-cell mitogen Salmonella typhimurium mitogen (STM), as well as for their ability to lyse (51)Cr-labelled YAC-1 cells. The spleen and other lymphoid organs were also examined histopathologically and differential white blood cell counts were done. Cells from animals treated with cyclosporin A showed a dose-dependent reduction in the proliferative response to Con A and, to a lesser extent, to PHA, but not to STM. In contrast, natural killer activity, measured by YAC-1 cell lysis, increased with greater cyclosporin A dosage. Histological examination of spleen and lymph nodes also revealed changes at all doses, particularly in T-dependent areas. White blood cell counts were largely unaffected. Thus, while in vitro immune function tests did not prove to be necessary for the identification of potential immunotoxicity in this model, they provided valuable information about possible mechanisms and guidance for further investigations.