Pathology of the thymus: changes induced by xenobiotics and gene targeting

Studies on the thymus in pathologic conditions have been of great help in the elucidation of the function of the organ in T-cell development. The first examples come from congenital immunodeficiency states in man and laboratory animals. A number of toxic substances affect different components of the thymus already at exposure levels where there is no effect on the peripheral immune system. In some cases, this thymotoxic effect has been causally related to defects in the peripheral immune system (immunodeficiency and autoimmunity). In recent years immunodeficient states have been created in mouse by disruption of genes coding immunologically relevant molecules. Studies on such gene 'knock-out' mice have shown that a number of molecules are indispensable for appropriate T-cell development at different stages in the thymus, whereas others are dispensable. It is concluded that the experimental approach combining gene targeting and exposure to thymotoxic xenobiotics will present interesting tools for further studies in thymus research.