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 m an and laboratory animals. A number of toxic substances affect differe nt components of the thymus already at exposure levels where there is no effect on the peripheral immune system. In some cases, this thymoto xic effect has been causally related to defects in the peripheral immu ne system (immunodeficiency and autoimmunity). In recent years immunod eficient states have been created in mouse by disruption of genes codi ng immunologically relevant molecules. Studies on such gene 'knock-out ' mice have shown that a number of molecules, are indispensable for ap propriate T-cell development at different stages in the thymus, wherea s others are dispensable. It is concluded that the experimental approa ch combining gene targeting and exposure to thymotoxic xenobiotics wil l present interesting tools for further studies in thymus research.