The thymus and self-tolerance: co-existence of encephalitogenic S100 beta-specific T cells and their nominal autoantigen in the normal adult rat thymus.

Abstract

The adoptive transfer of auto-reactive T cells specific for S100 beta protein mediates experimental autoimmune panencephalomyelitis, an inflammatory autoimmune disease of the nervous system and eye. However, unlike classical encephalitogenic autoantigens which are components of the myelin membrane and restricted to the nervous system, S100 beta is expressed by many different cell types in a wide variety of peripheral tissues. We now report that S100 beta is also expressed within the rat thymus from embryonic day 16 through to adulthood at which time point the protein is localized within stroma cells of the thymic medulla. However, despite the continued expression of this autoantigen within the thymic microenvironment it proved possible to isolate encephalitogenic, S100 beta-specific CD4+ alpha beta TCR T cell lines from the naive adult rat thymus. These T cell lines were highly specific for S100 beta, and following activation in vitro and adoptive transfer initiate an inflammatory response in the central nervous system and eye of naive syngeneic recipients. These observations provide additional evidence that clonal deletion of autoaggressive T cell clones in the thymus is leaky. In this case allowing potentially autoaggressive T cell clones specific for S100 beta, a non-myelin autoantigen expressed in the nervous system, thymus and many peripheral tissues, to become an intrinsic component of the normal immune repertoire.