ABSTRACT
Thymic deletion ensures T cell tolerance towards ubiquitous antigens expressed in the thymus as well as to blood-borne antigens taken up by thymic and circulating antigen presenting cells (APCs). In addition, it has been shown that low levels of certain peripheral tissue antigens are expressed in the thymus (1,2), thus inducing deletion of high affinity T cells specific for these antigens. Despite these mechanisms, T cells reactive to tissue-specific antigens, such as pancreatic β-cell antigens, can mature and enter the circulation. Activation of such autoreactive T cells can lead to autoimmunity and result in tissue destruction and functional impairment. Although over the recent years knowledge has accumulated concerning possible target antigens and genes involved in several autoimmune diseases, we still remain fairly ignorant of the initial events leading to the triggering of an autoimmune response as well as the precise mechanisms by which T cells induce tissue damage. In the present chapter, we will discuss results obtained with experimental murine models developed in our and other laboratories, which have contributed to a better understanding of autoimmune phenomena.
