T-cell Education


     Immature lymphocytes formed in the bone marrow are released into the circulatory system. Some of these which are to become T-cells must first undergo selection based on specificity and degree of response to antigens.

This occurs within the thymus gland, located in the cardiothoracic cavity above the heart.

   Within the thymus, pre T-cells migrate to the sub-capsular region.

    These cells then divide rapidly, and pass into the cortex. At this time each will produce its particular diversified T-cell receptor.

   This pre T-cell must also generate two other receptors, CD8 and CD4, which will enable it to bind to the major histocompatibility complex molecules which present antigenic peptides.

   All these cells are termed thymocytes.

They now migrate deeper into the cortex, and pass among large numbers of epithelial cells which have MHC class I and II molecules on their surface.

   It is the CD8 receptor, together with the T-cell receptor, which may bind to the MHC class I molecule. Alternatively, binding could occur through the CD4 receptor, with MHC class II molecules.

   Cells which fail to bind to either MHC molecule type die by apoptosis because they are not given the signal necessary to rescue them. A large proportion of thymocytes are lost at this stage, which is termed positive selection.

    Surviving cells continue towards the medulla. Interdigitating cells present them with antigens belonging to the body. Those which bind too strongly are destroyed. This is called negative selection.

    The cells which do survive, possibly less than 1% of the original population, now shed their non-functional MHC receptor - CD4 or CD8.

Those which respond to MHC class I with the CD8 receptor lose the CD4 group. Conversely, thymocytes which bind with MHC class II through CD4, lose their CD8 group. They are now mature T-cells.

    The educated T-cells pass through the medulla back into the circulation.

    The blood stream carries the T-cells to the secondary lymphatic tissues, where they remain until stimulated by antigen, presented on antigen presenting cells.