T cell
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T cells belong to 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 NK cells by the presence of a special receptor on their cell surface that is called the T cell receptor (TCR). The abbreviation "T", in T cell, stands for thymus since it is the principal organ for their development.
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[edit] T cell subsets
Image:TCR-MHC bindings.png Several different subsets of T cells have been described, each with a distinct function.
- Cytotoxic T cells (Tc cells) 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.
- Helper T cells, (Th cells) are the "middlemen" of the adaptive immune system. Once activated, they divide rapidly and secrete small proteins called cytokines that regulate or "help" the immune response. These cells (also called CD4+ T cells) are a target of HIV infection; the virus infects the cell by using the CD4 protein to gain entry. The loss of Th cells as a result of HIV infection leads to the symptoms of AIDS.
- Regulatory T cells (Treg 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 towards the end of an immune reaction. Typically, these 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 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 MHC molecules, NKT cells recognize glycolipid antigen presented by a molecule called CD1d. Once activated, these cells can perform functions ascribed to both Th and Tc cells (i.e. cytokine production and release of cytolytic/cell killing molecules).
- γδ T cells represent a small subset of T cells that possess a distinct 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 unknown. However, γδ T cell do not seem to be MHC restricted and are unique in that they 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.
[edit] T cell development
All T cells ultimately derive from haematopoietic stem cells in the bone marrow. Hematopoietic progenitors derived from haematopoietic stem cells populate the thymus and expand by cell division to generate a large population of immature "thymocytes".<ref>Schwarz BA, Bhandoola A. Trafficking from the bone marrow to the thymus: a prerequisite for thymopoiesis. Immunol Rev 209:47, 2006. full text</ref> 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, while the other 2% survive and leave the thymus to become mature immunocompetent T cells.
[edit] Positive selection
Double positive T cells 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 T cells which bind the MHC/antigen complex with adequate affinity will receive a vital "survival signal." The other T cells die by apoptosis (programmed cell death) and their remains are engulfed by macrophages. This process is called positive selection.
[edit] Negative selection
Cells 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 the dendritic cells and macrophages. If the T cells interact too strongly with the antigen, they will also die by apoptosis. This process is called negative selection — an important mechanism of immunological tolerance that prevents the formation of self-reactive T cells that may generate autoimmune disease in the host.
[edit] T Cell Activation
Although the specfic mechanisms of activation vary slightly between different types of T cells, the following two-signal model is generally true for most:
- The interaction between TCR molecules and specific MHC/antigen complexes on APCs delivers signal 1 into the T cell.
- Costimulatory interactions between CD28 molecules on the T cell and B7 molecules on the APC deliver signal 2, activating the T cell. Without costimulation a T cell will become functionally inert (anergic).
T cell activation can be gauged by measuring proliferation, usually by incorperation of radioactive thymidine, or secretion of IL-2, an event which is dependent on costimulation.
[edit] See Also
[edit] References
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[edit] External links
- T cells and Antigens Animation
- [1], Immunobiology, 5th edition, Janeway, Charles A.; Travers, Paul; Walport, Mark; Shlomchik, Mark. New York and London: Garland Publishing; c2001.
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