Most T lymphocytes of the immune system differentiate within the thymus along the CD4/CD8 developmental pathway by a highly ordered process termed thymic selection (
1 ,
2 ). The maturation status of thymocytes is commonly assessed by their expression of the coreceptor proteins CD4 and CD8 and their surface density of aβ T cell receptors (αβ TCR), (
1 ). Three major subpopulations of T cells exist within the thymus that exemplify the progression of thymocytes along the CD4/CD8 developmental pathway:
1. |
CD4 − CD8 − (double-negative) thymocytes which express no αβ TCR; |
2. |
CD4 + CD8 + (double-positive) thymocytes, which express no/low αβ TCR; and |
3. |
CD4 + CD8 − and CD4 − CD8 + (single positive) thymocytes, both of which express high surface density of αβ TCR ( 1 – 4 ), (Fig. 1 ). |
Fig. 1. Intrathymic development of thymocytes along the CD4/CD8 developmental pathway. Immature CD4 − CD8 − thymocytes develop into progeny CD4 + CD8 + thymocytes which maintain low expression of αβTCR. Immature CD4 + CD8 + thymocytes expressing αβTCR of appropriate specificities are selected for further differentiation into mature T cells that express either CD4 (CD4 + CD8 − ) or CD8 (CD4 − CD8 + ) coreceptor molecules, but not both. Mature CD4 + CD8 − and CD4 − CD8 + thymocytes emigrate from the thymus to the periphery where they may localize in lymphoid organs (for example, lymph node or spleen).