IMP Research Report 2002

developmental pathways of thymus epithelium. One of
our long-term goals is to test whether transplantation
of genetically modified thymic epithelial cells can be of
therapeutic benefit in autoimmunity.
Figure 2: During their maturation in the thymus, developing T cells
migrate from the outer cortex to the medulla. On their way, they can
make contact with various types of thymic stromal cells. We want to
understand how these interaction partners and the differentiation
stage at which self-antigen is encountered determine the
developmental fate of autoreactive T cells.
predominantly cover abundant or ubiquitous selfantigens,
while tolerance to the universe of tissuespecific
proteins, whose restricted expression pattern
precludes presentation in the thymus, would rely on
post-thymic, “peripheral” mechanisms. However, this
concept has been called into question by the emerging
notion that numerous “tissue-specific” antigens are
expressed within the thymus and displayed here for
repertoire selection. We found that this „promiscuous“
gene expression is a particular feature of medullary
thymic epithelial cells (mTEC). The physiological
importance of this phenomenon is underscored by
Figure 3: Visualization by in situ hybridization of two cells
expressing a „liver-specific“ antigen in a medullary region of the
thymus (C = cortex; M = medulla)
Contact: klein@imp.univie.ac.at
findings that allelic- or strain-dependent variations in
the intrathymic expression-levels of certain tissueantigens
correlate with the susceptibility to organspecific
autoimmunity. Along the same lines, we found
that absence of central tolerance to a particular epitope
of a Central Nervous System (CNS)-autoantigen due
to intrathymic expression of a truncated splice-variant
influenced the susceptibility to CNS-specific
autoimmunity in mice. One focus of our interest is to
understand the mechanism(s) underlying the
expression of tissue-specific antigens and how this
relates to the development of thymus epithelial cells.
We are performing a detailed analysis of the phenotype
of thymic epithelial cells in normal and mutant mice, in
order to compare global gene expression profiles in
various subsets of these cells and to elucidate
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