Mature T Cells Develop from Lymphoid Stem Cells That Have Migrated to the Thymus
Lymphoid stem cells that are destined to become T cells migrate to the thymus and are referred to as thymocytes. (The thymus extends approximately from the base of the trachea to the front of the heart.) The most recent immigrants from bone marrow arrive at the cortex of the thymus and lack important cell surface markers, such as T ccll receptors (TCRs), CD4» and CD8 markers, which are essential for T-cell activation.
These immature thymocytes undergo a highly complex and tightly regulated development and maturation process into mature T cells. During development the cells begin to acquire both CD4 and CD8 surface markers (double positive) and TCRs. As the cells further mature, they lose either CD4 or CD8 markers. CD4+∕CD8+ cells that lose the CD8 marker become CD4+∕CD8^ cells and are known as T-helper cells, whereas those double-positive cells that lose the CD4 marker become CD4^∕CD8+ cells, or cytotoxic T cells.The selection for survival of T cells during this developmental process is extremely stringent and discriminating. During development the thymocytes learn two important lessons: (I)T cells respond only to foreign antigens (positive selection), and (2) the cells will not respond to “self” antigens (negative selection). Learning these two critical lessons is essential for the survival of the organism. Therefore, any developing thymocytes that deviate from learning these two key lessons are terminated by apoptosis (negative selection). Consequently, greater than 90% of developing thymocytes die within the thymus. Cells that are marked for intrathymic death include those cells that are defective (i.e., cannot bind to antigens or have truncated receptors) or autoreactive (bind strongly to “self” peptides). Thus, only competent, positively selected T cells (CD4, or CD8‘) arc allowed to emigrate out of the thymus as T cells.