[en] Before reacting against non-self infectious agents, the immune system is
educated to tolerate the host molecular structure (self). The induction of self-tolerance is
a multistep process that begins in the thymus during fetal ontogeny (central tolerance)
and also involves inactivating mechanisms outside the thymus (peripheral tolerance).
The thymus is the primary lymphoid organ implicated in the development of competent
and self-tolerant T cells. During ontogeny, T cell progenitors originating from
hemopoietic tissues (yolk sac, fetal liver, and then bone marrow) enter the thymus and undergo a program of
proliferation, T cell receptor (TCR) gene rearrangement, maturation and selection. Close interactions between
thymocytes (pre-T cells) and the thymic cellular environment are crucial both for T cell development and
induction of central self-tolerance. Thymic epithelial and stromal cells synthesize polypeptides belonging to
various neuroendocrine families. The thymic repertoire of neuroendocrine-related precursors transposes at the molecular level the dual role of the thymus in T cell negative and positive selection. Thymic precursors not only constitute a source of growth peptides for cryptocrine signaling between thymic stromal cells and pre-T cells, but are also processed in a way that leads to the presentation of self-antigens by thymic major
histocompatibility complex (MHC) proteins. Thymic neuroendocrine self-antigens often correspond to
peptide sequences highly conserved during the evolution of their corresponding family. The thymic
presentation of some neuroendocrine self-antigens is not restricted by MHC alleles. Following the
presentation of neuroendocrine self-antigens by thymic MHC proteins, the T cell system might be educated to
tolerate main hormone families. Recent experiments argue that a defect in the thymic essential tolerogenic
function is implicated as an important factor in the pathophysiology of many autoimmune diseases.
