T-helper cells are so named because they produce and secrete protein molecules called cytokines that perform various functions within the immune system that direct and 'help' the immune response. Within the Helper T-cell group are two further subsets known as Th1 (or type 1) and Th2 (or type 2). Cytotoxic T-cells play a central role in the destruction of tumour cells and virally-infected cells, and are also thought to have an important role in transplant rejection.
Differentiation of T-cells into CD4+ and CD8+ cells begins in the thymus during T-cell development. However, cells only become fully differentiated mature cells in the peripheral lymphoid system, during an active immune response.
All T-cells originate in the marrow of long bones (such as the femur), and are derived from hematopoetic stem cells. Hematopoetic progenitors that derive from these stem cells travel to the thymus via the lymphatic system. Upon reaching the thymus they divide to generate T-cell precursors known as immature thymocytes (Schwarz B A, Bhandoola A. 2006). Approximately 98% of these precursor cells die in the thymus without becoming fully-differentiated T-cells, due to selection processes called positive and negative selection. The 2% of cells that survive selection eventually leave the thymus to become mature T-cells.
At the beginning of the selection process, all thy...
Thymocytes that bind the MHC-antigen complex with sufficient affinity (binding strength) are allowed to survive and move to the next stage of development. Thymocytes which do not bind with adequate affinity receive a chemical signal which causes them to undergo apoptosis, a process also known as programmed cell death, in which cells die in a way that cannot cause harm to the host. This first round of selection is called positive selection, because cells which bind with affinity are allowed to survive. During this process another type of selection occurs: cells which bind with MHC class II molecules develop into CD4+ cells, and cells which bind with MHC class I molecules develop into CD8+ cells.
Those cells that survive the first round of selection migrate to the boundary between the cortex and medulla of the thymus. In the medulla, they are presented again with MHC molecules that present self-antigens. This time, the complex is presented by dendritic cells and macrophages, two types of antigen-presenting cells. In this situation, cells which bind with very strong affinity receive a death-inducing signal, and undergo apoptosis, while cells that do not bind with strong affinity are allowed to survive and continue development. It is at this stage, called negative selection, that the majority of developing T-cells die. Negative selection is a particularly important part of the development process, as it prevents the development of T-cells which react to self-antigens, and thus prevents the development of auto-immune disease (Baldwin TA, 2004). The cells that survive both positive and negative selection are mature nave T-cells, which then leave the thymus and begin to circulate in the lymphatic