The Le Douarin phenomenon: a shift in the paradigm of developmental self-tolerance.

Ever since the foundations of Immunology, "self-tolerance" has remained a central issue in this field, pertaining to basic and clinical questions alike. Burnet and Medawar shared the Nobel Prize in 1960 for proposing that tolerance is induced by tissue antigens, if present during the development of the immune system during the embryonic/neonatal period. Very elegant experiments by Le Douarin and colleagues in the 1980's demonstrated that this is not the case; rather, the establishment of tolerance to peripheral tissues requires thymic epithelium which selects CD4 T lymphocytes mediating "dominant tolerance". The recent wealth of work on "regulatory T cells", as well as observations on the selective regulation of "tissue-specific" gene expression in thymic epithelial cells, confirm the critical relevance of those seminal findings in modern immunology.