Even when the TCR has not yet been synthesized, this CD3 molecule is already present in the cytoplasm of the cell. The receptor is then expressed on the cell membrane with the CD 3 molecule, which acts as the transmembrane signaltransducing molecule after TCR stimulation. Only after this gene rearrangement is completed can the cell synthesize the receptor. This process of gene rearrangement requires the thyme microenvironment. Before transcription and translation into TCR become possible, combinations have to be made of gene segments encoding the variable and constant parts of the TCR. Upon entry, the DNA genomic organization encoding these chains is in germ line configuration, with a variety of gene segments encoding the variable part of the receptor molecule. This phenotypic change is accompanied by a crucial aspect of intrathymic T-cell maturation: the genesis of the TCR consisting of the α-β heterodimer. In the medulla, T cells have the phenotype of mature cells, with distinct CD4 + CD8 + (about 70%) and CD4 – CD8 + (about 30%) populations. Consider the CD4 and CD8 phenotypes: cells change from CD4 – CD8 – (double negative) at a very immature stage via a CD4 – CD8 + stage into a CD4 + CD8 + (double positive) phenotype, which is found on almost all lymphocytes in the cortex. These translocational stages in development are monitored on the basis of the immunologic phenotype. Finally, the cells move to the medulla, where they appear as medium-sized lymphocytes. They then pass through the cortex where the cells become small lymphocytes with scanty cytoplasm. The most immature cells, which enter the lobules by the blood vasculature at the corticomedullary junction, first move to the outer subcapsular cortex, where they appear as large lymphoblasts. The process of T-cell maturation includes a number of steps that are associated with location in different microenvironments. In congenitally athymic conditions (nude animals, children with the Di-George syndrome), the absence of a functionally active T-cell system is causally related to aplasia of the organ. The gland has a privileged function in promoting the maturation process. T cells reside in the thymus during their maturation from progenitor cells to immunocompetent T cells. Vos, in Handbook of Toxicologic Pathology (Second Edition), 2002 a.
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