T cell tolerance and autoimmunity.

Many T cells with auto-aggressive potential are deleted in the thymus. Although some of these escape to the general circulation, they do not usually damage organs such as the pancreas. To investigate the mechanisms preventing autoimmunity, we generated transgenic mice expressing known genes under the control of various promoters. We found that the occurrence of autoaggression depended on factors such as the precursor frequency of responding T cells, their state of activation, their accessibility to the autoantigen, the physicochemical properties of the autoantigen, the possibility of priming by environmental antigens which mimic the target antigen, and some inflammatory reaction in the target site.