Schematic diagram of the blood-thymus barrier. The blood-thymus barrier consists of three major elements: (1) capillary endothelium and its basal lamina, (2) perivascular connective tissue space occupied by macrophages, and (3) type I epithelioreticular cells with their basal lamina. The perivascular connective tissue is enclosed between the basal lamina of the epithelioreticular cells and the endothelial cell basal lamina. These layers provide the necessary protection to the developing immature T cells and separate them from mature immunocompetent lymphocytes circulating in the bloodstream.
macrophage developing T cells type I
, ... epithelioreticular basal lamina r n
@ endothelium pericyte epithelioreticular cell layer perivascular connective tissue capillary wall blood-- thymus barrier education (Fig. 13.28). This process is characterized by the expression and deletion of specific surface CD antigens.
The expression of CD2 and CD7 molecules on the cell surface indicates an early (double negative) stage of differentiation. This early stage is followed by the expression of the CD1 molecule, which indicates the middle stage of T cell differentiation. As maturation progresses, the cells express TCRs, CD3, and both CD4 and CD8 molecules (double-positive stage). These cells are then presented with self and foreign antigens by type II and III epithelioreticular cells. If the lymphocyte recognizes "self" MHC molecules and "self" or foreign antigen, it will survive (positive selection). If not, the cell will die. Cells that pass the positive selection test leave the cortex and enter the medulla. Here, they undergo another selection process in which cells that recognize "self" antigen displayed by self MHC are eliminated (negative selection). The cells that survive become either cytotoxic CD8+ T lymphocytes (by losing CD4 and retaining CD 8) or helper CD4+ T lymphocytes (by losing CD8 and retaining CD4). This stage is called the single-positive stage. Now the cells leave the thymus by passing from the medulla into the blood circulation. The process of thymic cell education is promoted by substances secreted by the epithelioreticular cells, including inter-leukins, colony stimulating factors, interferon y, thymosin, and thymopoietin.
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