T-CELL TOLERANCE AND AUTOIMMUNITY IN TRANSGENIC MODELS OF CENTRAL ANDPERIPHERAL TOLERANCE

Experiments with transgenic mice expressing genes encoding both antige ns in defined tissues and T-cell receptor genes of known specificities have enhanced our understanding of the mechanisms involved in the pat hogenesis of autoimmune states. They have also shed light on the means by which potentially autoreactive cells may be prevented from exertin g their autoaggressive potential. The value of the transgenic approach is that it can overcome the low frequency of peptide-specific T cells occurring in normal animals, and also provide a tissue-specific, cogn ate antigen that is absent in controls. These factors allow reactive T cells to be isolated or quantified by flow cytometry and their respon ses to antigen in vitro and in vivo be defined.