Thymus function and autoimmunity

PURPOSE: Thymus is the site of T-cell development and is essential for the induction of self-tolerance, by deletion of autoreactive T lymphocytes (negative selection) and by generation of regulatory T cells. Defect of the selection mechanism of both types of lymphocytes lead to autoimmune diseases. CURRENT KNOWLEDGE AND KEY POINTS: Elimination of potentially self-reactive T cells in the thymus requires the intrathymic expression of ubiquitous and "tissue-specific" antigens. Some thymic antigen expressions are dependent on AIRE expression. Mutations in the AIRE gene that are associated with the absence of autoantigen expression in the thymus, defects in the peptide presentation or in apoptosis can allow autoreactive T cells to escape negative selection, and are associated with autoimmune diseases. Recent data are now available concerning the thymic selection of autoreactive regulatory T cells. The Foxp3 gene was recently shown to be predominantly expressed in regulatory T cells and could be a more specific marker of regulatory T cells than phenotypic markers. FUTURE PROSPECTS AND PROJECTS: Animal models show that regulatory T cells injection or intrathymic inoculation of antigen lead to immunological tolerance in autoimmunity and transplantation. These novel strategies could be used in human.