T cells (also called T lymphocytes) are one of the major components of the adaptive immune system. Their roles include directly killing infected host cells, activating other immune cells, producing cytokines and regulating the immune response.
This article will discuss the production of T cells, the different types present in the immune system and relevant clinical conditions.
Production of T Lymphocytes
T lymphocytes originate from haematopoietic stem cells which are produced in the bone marrow. Some of these multipotent cells will become lymphoid progenitor cells that leave the bone marrow and travel to the thymus via the blood.
T lymphocytes undergo a selection process in the thymus, which the majority of developing T cells (called thymocytes) will not survive. Thymocytes that have receptors to self-antigen molecules receive negative signals and are removed from the repertoire.
Each T lymphocyte will develop its own T cell receptor (TCR) that is specific for a particular antigen. T lymphocytes that survive thymic selection will mature and leave the thymus. They will circulate through the peripheral lymphoid organs, ready to encounter a specific antigen and become activated. Once activated, the T cell will proliferate and differentiate into an effector T cell. The thymus atrophies as we age and so produces fewer naïve T lymphocytes over time.
T Lymphocyte types
Naïve T lymphocytes are are cells that have not yet encountered their specific antigen. In peripheral lymphoid organs naïve T lymphocytes can interact with antigen presenting cells (APCs), which use an MHC molecule to present antigen. If the T lymphocyte recognises a specific antigen, it will proliferate and differentiate into effector T lymphocytes of a particular type. Effector T lymphocytes will interact with host cells (rather than the pathogen) to carry out their immune function.
The cell either uses a co-receptor called CD8 or CD4 to bind to the MHC molecule. These proteins help us to differentiate major groups of effector T lymphocyte. Naïve T lymphocytes with CD8 will become cytotoxic T lymphocytes and those with CD4 will become T helper lymphocytes, each of which are specialised in particular tasks.
Cytotoxic T Lymphocyte
Cytotoxic T lymphocytes kill their target cells primarily by releasing cytotoxic granules into the cell to be killed. These cells recognise their specific antigen (such as fragments of viruses) when presented by MHC Class I molecules that are present on the surface of all nucleated cells.
MHC Class I molecules interact with a protein called CD8 on the cytotoxic T cells. Cytotoxic T cells require several signals from other cells to be activated, such as from dendritic cells and T helper cells.
Their main function is to kill virally infected cells, but they also kill cells with intracellular bacteria or tumorous cells.
T helper cells (Th) have a wider range of effector functions than CD8 T cells and can differentiate into many different subtypes, such as Th1, Th2, Th17 and regulatory T cells.
They become activated when they are presented with peptide antigens by MHC Class II molecules. These are expressed on the surface of APCs. MHC Class II molecules interact with a protein called CD4 on the T helper cells, which helps to identify this cell type.
The roles of a CD4 T cell may include activating other immune cells, releasing cytokines, and helping B lymphocytes to produce antibodies. They help to shape, activate and regulate the adaptive immune response.
Memory T Lymphocyte
Following an infection, antigen-specific, long-lived memory T lymphocytes are formed. Memory T lymphocytes are important because they can quickly proliferate into large numbers of effector T lymphocyte upon re-exposure to the antigen and have a low threshold for activation.
They provide the immune system with memory against previously encountered antigens. Memory T lymphocytes may either be CD4+ or CD8+.
Clinical Relevance – Severe Combined Immune Deficiency (SCID)
SCID is a group of primary immunodeficiencies with defects in both T and B cell numbers and/or function. Individuals with SCID are prone to recurrent infections, sepsis and failure to thrive.
SCID can result from defects in many genes, although the most common defect is X-linked.
The best treatment for SCID is a bone marrow transplant.