T Cell Development and Function

Immature T cells develop in the bone marrow. Once they reach a certain stage of development, the leave the marrow and travel to the thymus, where they undergo the final—but most important—stage of development.

When they enter the thymus, immature T cells are capable of differentiating into any type of mature T cell (cytotoxic cells, regulatory cells, and helper cells). In addition, at this stage of their development they have not yet begun expressing the receptors that confer the antigenic specificity which mature T cells have.

During the development process, genes which code for T cell antigen receptors undergo a process of recombination. At the end of this process, the T cell is specific for an antigen—a sequence of around nine to eleven amino acids—and can only be activated by that specific antigen. Once this has been completed, the maturing T cells undergo a selection process in which T cells with a weak binding affinity for non-self antigen, and T cells with a strong binding affinity for self antigen, are eliminated

At the end of the maturation process, T cells exit the thymus and begin circulating in the blood and lymphatic systems until they are activated by antigen. As a result of maturation and selection, these cells are only capable of activating in the presence of foreign antigens (in cases where this process fails for some reason, an autoimmune disease, where the immune system attacks the body’s own tissues, may be the result).

Another important aspect of T cell development which occurs in the thymus is the differentiation of T cells into helper, cytotoxic, and regulatory T cells. Each type plays a very different role in the immune response.

Helper T cells are so-called because their principal function is the secretion of cytokines which control and direct the immune response.

Cytotoxic cells, on the other hand, have a more hands-on type of role, killing host cells which have been infected by intracellular pathogens such as viruses and parasites.

Regulatory cells (AKA suppressor T cells) are a subpopulation of T cells which do not play a role in the activation of the immune response against pathogens. Instead, their role is in suppressing the immune response against self antigen. The existence of this subpopulation was in doubt for many years, but recently research on regulatory cells has advanced to the point where their therapeutic potential in the treatment of autoimmune disease and transplant rejection are being explored.

When helper T cells are activated during the course of an immune response, they can develop into one of two types of cells: type 1 helper cells, and type 2 helper cells.

The factors that determine what type of helper cell is activated are not fully understood. However, it has long been known that each type of cell is associated with different arms of the immune response, and that each helper cell type stimulates the response which is most effective at eliminating the pathogen involved.

Each helper cell type stimulates the required response by secreting a particular pattern of cytokines, to stimulate and enhance the activity of immune cells which can effectively fight the infection.

Type 1 helper cells secrete cytokines such as interferon-gamma, which improves the killing efficiency of macrophages, and improves the proliferation efficiency of cytotoxic T cells. This type 1 immune response is produced as a result of infection with viruses and other intracellular pathogens.

Type 2 helper cells secrete a wide range of interleukins, which stimulate proliferation of B cells, and stimulate antibody production. This type 2 response is produced in response to extracellular bacteria and toxins.

In both cases, the activation of helper T cells, and therefore the activation of the adaptive immune response, stimulates the development of immunological memory, which provides protection for the body the next time the same pathogen is encountered.