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 shall discuss the production of T cells, the different types present in the immune system and relevant clinical conditions.
Production of T Cells
T cells originate from haematopoietic stem cells which are produced in the bone marrow. Some of these multipotent cells will becomes progenitor cells that leave the bone marrow and travel to the thymus via the blood. In the thymus these cells mature: T cells are named after their thymus-dependent development.
T cells undergo a selection process in the thymus, which the majority of developing T cells (called thymocytes) will not survive. Thymocytes that interact with self-MHC molecules receive positive signals for survival, and thymocytes that have receptors to self-antigen receive negative signals and are removed from the repertoire.
Each T cell will develop its own T cell receptor (TCR) that is specific for a particular antigen. T cells that survive thymic selection will mature and leave the thymus. They will circulate through the peripheral lymphoid organs, each ready to encounter a specific antigen and be activated. Once activated, the T cell will proliferate and differentiate into an effector T cell.
The thymus involutes as we age and so produces fewer naïve T cells over time. This means that older people have reduced T cell diversity, which contributes to the increased susceptibility to infections seen with age.
Types of T-Cells
Naïve T cells are are cells that have not yet encountered their specific antigen. In peripheral lymphoid organs naïve T cells can interact with antigen presenting cells (APCs), which use an MHC molecule to present antigen. If the T cell recognises a specific antigen, it will proliferate and differentiate into effector T cells of a particular type. Effector T cells 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 cells. Naïve T cells with CD8 will become cytotoxic T cells and those with CD4 will become T helper cells, each of which are specialised in particular tasks.
Cytotoxic T Cells (CD8 T Cells)
Cytotoxic T cells 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, which helps to identify this cell type. 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) (CD4 T Cells)
T helper cells 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, which 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 cells to produce antibodies. They help to shape, activate and regulate the adaptive immune response.
Memory T Cells
Following an infection, antigen-specific, long-lived memory T cells are formed. Memory T cells are important because they can quickly expand to large numbers of effector T cells 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 cells 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, failure to thrive and if untreated, are likely to die within the first few years of life.
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, which is most effective if carried out in the first three months of life.