CD8+ T cells (commonly known as cytotoxic T cells) are cells of the immune system that contribute to the body's adaptive immune response. These immune cells are characterized by a CD8 protein on their cell surface that allow them to recognize, bind and kill cells infected by intracellular bacteria, intracellular viruses and cancer cells. They are developed in the bone marrow and thymus, and are regulated by transcription factors and signalling components. CD8+ T cells have also been found to play various roles in different diseases.
CD8+ T cells are developed in the bone marrow and thymus. The first step occurs in the bone marrow, where hematopoietic stem cells are made into lymphoid progenitor cells. These lymphoid progenitor cells will then move to the thymus, where they will be made into naïve CD8+ T cells. These naïve CD8+ T cells will then move into the blood and circulate around the body.
CD8+ T cells are characterized by a CD8 protein on their cell surface that functions to recognize and bind infected cells. The CD8 protein is composed of a CD8α and CD8β chain; Each CD8 protein has a molecular weight of around 34 kDa. Infected nucleated cells will present MHC Class I molecules on their cell surface. The CD8 chain on the naïve CD8+ T cell will recognize peptides presented by these MHC Class I molecules, and thus will allow the CD8+ T cell to bind to infected cells. Once bound, the naïve CD8+ T cell will become mature CD8+ T cell through regulatory mechanisms discussed in the next section.
Function and regulation
When the body is infected by a pathogen, naïve CD8+ T cells will recognize and bind infected cells through the recognition of MHC Class I peptides on infected cells by the CD8 protein on CD8+ T cells, as previously mentioned. Once bound, CD8+ T cells will kill infected cells by secreting perforin (a pore-forming protein) and granzymes (a protease) onto infected cells. The pores formed by perforin disrupts the protective barrier of the infected cell membrane, and will enable influx of ions and water into the cell, and efflux of essential nutrients, substances and proteins out of the cell - ultimately destroying the integrity of the cell. Furthermore, the granzymes will induce programmed cell death in the infected cell. Overall, this mechanism of destruction using perforin and granzymes is a similar process to how Natural Killer (NK) cells destroy cells infected by intracellular viruses and cancer cells.
The transcription factor Eomesodermin is suggested to play a key role in CD8+ T cell function, acting as a regulatory gene in the adaptive immune response. Studies investigating the effect of loss-of-function Eomesodermin found that a decrease in expression of this transcription factor resulted in decreased amount of perforin produced by CD8+ T cells.
Furthermore, maturation of naïve T cells to mature CD8+ T cells is mediated by both T helper cells and CD40 signalling. Once the naïve CD8+ T cell is bound to the infected cell, the infected cell is triggered to release CD40. This CD40 release, with the aid of helper T cells, will trigger differentiation of the naïve CD8+ T cells to mature CD8+ T cells.
Roles in certain diseases
CD8+ T cells have been found to play different roles in certain diseases, such as in HIV infection and in Type 1 diabetes. HIV over time has developed many strategies to evade the host cell immune system. For example, HIV has adopted very high mutation rates to allow them to escape recognition by CD8+ T cells. They are also able to down-regulate expression of surface MHC Class I proteins of cells that they infect, in order to further evade destruction by CD8+ T cells. If CD8+ T cells cannot find, recognize and bind to infected cells, the virus will not be destroyed and will continue to grow. Furthermore, it has been recently discovered that CD8+ T cells play a critical role in Type 1 diabetes. It was previously thought that this autoimmune disease was exclusively controlled by CD4+ cells - but recent studies in a diabetic mouse model showed that CD8+ T cells also engaged in the destruction of insulin-producing pancreatic cells.
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