T-lymphocytes, or thymocytes, are produced in the bone marrow and undergo maturation in the thymus during the first trimester of gestation.  In the thymus the processes of T-cell receptor (TCR) gene rearrangement, positive selection, negative selection and expression of extracellular membrane markers and co-stimulatory molecules occur.  Pro-T cells arrive at the thymus as "double negative" cells - cells that lack both CD4 and CD8 antigens.  Next, the process of TCR gene rearrangement begins first with rearrangement of the b chain genes.  Synthesis of a productive rearrangement of the b chain of the TCR leads to stimulation of production of BOTH CD4 and CD8 antigens with simultaneous expression of BOTH CD4 and CD8.  These cells are referred to as "double positive" T cells or immature T-lymphocytes (Choice A).  Subsequently, the process of rearrangement of the a chain of the TCR occurs followed by positive selection in the thymic cortex and negative selection in the thymic medulla.  Once these processes are complete, the final step in maturation of the T-lymphocytes is loss of either the CD4 or the CD8 antigen so that the mature thymocytes only express one or the other of these antigens.

(Choice B)  Mature cytotoxic T lymphocytes (CTLs) are also referred to as CD8+ T-lymphocytes; these cells do not express the CD4 antigen on their surfaces.  These cells recognize and kill altered self cells by recognizing foreign antigen presented by these cells on MHC Class I molecules on the cell surface.

(Choice C)  Mature helper T lymphocytes are also referred to as CD4+ T-lymphocytes; these cells do not express the CD8 antigen on their surfaces.

(Choice D)  Antigen presenting cells include dendritic cells, macrophages and B-lymphocytes.  Dendritic cells are professional antigen presenting cells.  They take up antigen by endocytosis, constitutively express MHC Class II and the co-stimulatory B7 molecule, and are able to activate all forms of T cells (naïve, effector and memory).  Macrophages are phagocytes that only inducably express MHC II and B7 and can only activate effector and memory T cells, not naive T cells.  B-lymphocytes take up antigen by receptor-mediated (membrane-bound antibody) endocytosis and constitutively express MHC II.  These cells are able to stimulate all forms of T-lymphocytes.

(Choice E)  Natural killer (NK) cells are part of the innate immune system and function in a fashion very similar to CD8+ CTLs though they express neither CD8 nor CD4 on their cell surfaces.

(Choice F)  Thymic epithelial cells play a role in positive selection of immature thymocytes in the thymic cortex.  These cells express MHC antigens on their cell surfaces that interact with the TCR on the immature thymocytes.  Thymocytes able to bind MHC receive a protective signal and do not undergo apoptosis, while thymocytes unable to bind MHC will be killed.  This is how self-MHC restriction is generated in the T-lymphocyte population.

Educational Objective:
Immature T-lymphocytes express both the CD4 and CD8 cell surface antigens in addition to a complete TCR or a pro-TCR.  These lymphocytes exist in the thymic cortex where they undergo positive selection and in the thymic medulla where they undergo negative selection.