T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocyte types, such as B cells and natural killer cells by the presence of a special receptor on their cell surface called T cell receptors (TCR). The abbreviation T , in T cell , stands for thymus, since this is the principal organ responsible for the T cell's maturation. Several different subsets of T cells have been discovered, each with a distinct function.
Types
Helper
T helper cells (T H cells) assist other white blood cells in immunologic processes, including maturation of B cells into plasma cells and activation of cytotoxic T cells and macrophages, among other functions. These cells are also known as CD4 + T cells because they express the CD4 protein on their surface. Helper T cells are presented peptide antigens associated with MHC class II on the surface of Antigen Presenting Cells (APCs). Once activated, they divide rapidly and secrete small proteins called cytokines that regulate or assist in the immune response. These cells can differentiate into one of several subtypes, including T H 1, T H 2, T H 3, T H 17,T FH , or others, which secrete different cytokines to facilitate a different type of immune response. The mechanism by which T cells are directed into a particular subtype is poorly understood, though signalling patterns from the APC are thought to play an important role.
Cytotoxic
Cytotoxic T cells (T C cells, or CTLs) destroy virally infected cells and tumor cells, and are also implicated in transplant rejection. These cells are also known as CD8 + T cells since they express the CD8 glycoprotein at their surface. These cells recognize their targets by binding to antigen associated with MHC class I, which is present on the surface of nearly every cell of the body. Through IL-10, adenosine and other molecules secreted by regulatory T cells, the CD8 + cells can be inactivated to an anergic state, which prevent autoimmune diseases such as experimental autoimmune encephalomyelitis.
Memory
Memory T cells are a subset of antigen-specific T cells that persist long-term after an infection has resolved. They quickly expand to large numbers of effector T cells upon re-exposure to their cognate antigen, thus providing the immune system with "memory" against past infections. Memory T cells comprise two subtypes: central memory T cells (T CM cells) and effector memory T cells (T EM cells). Memory cells may be either CD4 + or CD8 + .
Regulatory
Regulatory T cells (T reg cells), formerly known as suppressor T cells , are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus. Two major classes of CD4 + regulatory T cells have been described, including the naturally occurring T reg cells and the adaptive T reg cells. Naturally occurring T reg cells (also known as CD4 + CD25 + FoxP3 + T reg cells) arise in the thymus, whereas the adaptive T reg cells (also known as Tr1 cells or Th3 cells) may originate during a normal immune response. Naturally occurring T reg cells can be distinguished from other T cells by the presence of an intracellular molecule called FoxP3. Mutations of the FOXP3 gene can prevent regulatory T cell development, causing the fatal autoimmune disease IPEX.
Natural killer
Natural killer T cells (NKT cells) are a special kind of lymphocyte that bridges the adaptive immune system with the innate immune system. Unlike conventional T cells that recognize peptide antigen presented by major histocompatibility complex (MHC) molecules, NKT cells recognize glycolipid antigen presented by a molecule called CD1d. Once activated, these cells can perform functions ascribed to both T h and T c cells (i.e., cytokine production and release of cytolytic/cell killing molecules). They are also able to recognize and eliminate some tumor cells and cells infected with herpes viruses.
γδ
γδ T cells (gamma delta T cells) represent a small subset of T cells that possess a distinct T cell receptor (TCR) on their surface. A majority of T cells have a TCR composed of two glycoprotein chains called α- and β- TCR chains. However, in γδ T cells, the TCR is made up of one γ-chain and one δ-chain. This group of T cells is much less common (5% of total T cells) than the αβ T cells, but are found at their highest abundance in the gut mucosa, within a population of lymphocytes known as intraepithelial lymphocytes (IELs). The antigenic molecules that activate γδ T cells are still widely unknown. However, γδ T cells are not MHC restricted and seem to be able to recognise whole proteins rather than requiring peptides to be presented by MHC molecules on antigen presenting cells. Some recognize MHC class IB molecules though. Human Vγ9/Vδ2 T cells, which constitute the major γδ T cell population in peripheral blood, are unique in that they specifically and rapidly respond to a small non-peptidic microbial metabolite, HMB-PP, an isopentenyl pyrophosphate precursor.
Development in the thymus
See Thymocyte for review of thymic selection
All T cells originate from hematopoietic stem cells in the bone marrow. Hematopoietic progenitors derived from hematopoietic stem cells populate the thymus and expand by cell division to generate a large population of immature thymocytes. The earliest thymocytes express neither CD4 nor CD8, and are therefore classed as double-negative (CD4 - CD8 - ) cells. As they progress through their development they become double-positive thymocytes (CD4 + CD8 + ), and finally mature to single-positive (CD4 + CD8 - or CD4 - CD8 + ) thymocytes that are then released from the thymus to peripheral tissues.
About 98% of thymocytes die during the development processes in the thymus by failing either positive selection or negative selection , whereas the other 2% survive and leave the thymus to become mature immunocompetent T cells.
The thymus contributes more naive T cells at younger ages. As the thymus shrinks by about 3% a year throughout middle age, there is a corresponding fall in the thymic production of naive T cells, leaving peripheral T cell expansion to play a greater role in protecting older subjects.
Positive selection
Positive selection "selects for" T-cells capable of interacting with MHC. Double-positive thymocytes (CD4 + /CD8 + ) move deep into the thymic cortex where they are presented with self-antigens (i.e., antigens that are derived from molecules belonging to the host of the T cell) complexed with MHC molecules on the surface of cortical epithelial cells. Only those thymocytes that bind the MHC/antigen complex with adequate affinity will receive a vital "survival signal." Developing thymocytes that do not have adequate affinity cannot serve useful functions in the body (i.e. the cells must be able to interact with MHC and peptide complexes in order to effect immune responses). Because of this, the thymocytes with low affinity die by apoptosis and are engulfed by macrophages.
A thymocyte's fate is also determined during positive selection. Double-positive cells (CD4 + /CD8 + ) that are positively selected on MHC class II molecules will eventually become CD4 + cells, while cells positively selected on MHC class I molecules mature into CD8 + cells. A T cell becomes a CD4 + cell by downregulating expression of its CD8 cell surface receptors. If the cell does not lose its signal through the ITAM pathway, it will continue downregulating CD8 and become a CD4 + , single positive cell. But if there is signal drop, the cell stops downregulating CD8 and switches over to downregulating CD4 molecules instead, eventually becoming a CD8 + , single positive cell.
This process does not remove thymocytes that may cause autoimmunity. The potentially autoimmune cells are removed by the process of negative selection (discussed below).
Negative selection
Negative selection removes thymocytes that are capable of strongly binding with "self" peptides presented by MHC. Thymocytes that survive positive selection migrate towards the boundary of the thymic cortex and thymic medulla. While in the medulla, they are again presented with self-antigen in complex with MHC molecules on antigen-presenting cells (APCs) such as dendritic cells and macrophages. Thymocytes that interact too strongly with the antigen receive an apoptotic signal that leads to cell death. The vast majority of all thymocytes end up dying during this process. The remaining cells exit the thymus as mature naive T cells. This process is an important component of immunological tolerance and serves to prevent the formation of self-reactive T cells that are capable