Thymocytes experience four main processes before maturing. The entry of thymocytes into the thymus, the generation of double-positive thymocytes in the cortex, the positive selection of thymocytes in the cortex and the negative selection of thymocytes in the medulla, and the export of mature T-cells from the thymus to peripheral tissues. The negative selection of thymocytes depends on the expression of self-antigens by medullary thymic epithelial cells (MECs). The autoimmune regulator (AIRE) is a transcription factor, which turns on the expression of these self-antigens in the MECs and therefore, defects in the AIRE protein can result in autoimmunity (Metzger and Anderson, 2011). Specifically, mutations in the gene that encode for the AIRE protein have been linked to type I autoimmune polyendocrinopathy (Shikama et al., 2009).
Development of T-cells
T-cells are a type of lymphocyte that play a major role in cell-mediated immunity and provide an immunological memory of previously encountered pathogens. T-cells arise from hematopoetic stem cells in the bone marrow and then go on to populate the thymus, which is why they are called T-cells. Thymocytes enter the thymus and begin to proliferate and generate a large population of T-cells. As they progress through development they go through positive selection in the cortex and negative selection in the medulla before reaching maturation and finally leaving to surrounding tissues. During positive selection double-positive thymocytes (CD4+/CD8+) are exposed to self-antigens on MHC-I and MHC-II of cortical epithelial cells. Only the thymocytes that bind to MHC-I or -II appropriately are able to continue cell development into the medulla where they undergo negative selection. While in the ...
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