International Immunology, Vol 9, 897-904, Copyright © 1997 by Oxford University Press
K Kojima, M Reindl, H Lassmann, H Wekerle and C Linington
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.
ARTICLES
The thymus and self-tolerance: co-existence of encephalitogenic S100 beta-specific T cells and their nominal autoantigen in the normal adult rat thymus
Department of Neuroimmunology, Max-Planck-Institute of Psychiatry, Martinsried, Germany.
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