language-icon Old Web
English
Sign In

T cell

A T cell is a type of lymphocyte which develops in the thymus gland and plays a central role in the immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor on the cell surface. These immune cells originate as precursor cells, derived from bone marrow, and develop into several distinct types of T cells once they have migrated in to the thymus gland - for which these cells are named. T cell differentiation continues even after they have left the thymus. A T cell is a type of lymphocyte which develops in the thymus gland and plays a central role in the immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor on the cell surface. These immune cells originate as precursor cells, derived from bone marrow, and develop into several distinct types of T cells once they have migrated in to the thymus gland - for which these cells are named. T cell differentiation continues even after they have left the thymus. Groups of specific, differentiated T cells have an important role in controlling and shaping the immune response by providing a variety of immune-related functions. One of these functions is Immune-mediated cell death, and it is carried out by T cells in several ways: CD8+ T cells, also known as 'Killer cells', are cytotoxic - this means that they are able to directly kill virus-infected cells as well as cancer cells. CD8+ T cells are also able to utilize small signalling proteins, known as cytokines, to recruit other cells when mounting an immune response. A different population of T cells, the CD4+ T cells, function as 'Helper cells'. Unlike CD8+ Killer T cells, these CD4+ Helper T cells function by indirectly killing cells identified as foreign: they determine if and how other parts of the immune system responds to a specific, perceived threat. Helper T cells also use cytokine signalling to influence regulatory B cells directly, and other cell populations indirectly. Regulatory T cells are yet another distinct population of these cells that provide the critical mechanism of tolerance, whereby immune cells are able to distinguish invading cells from 'self' - thus preventing immune cells from inappropriately mounting a response against oneself (which would by definition be an 'autoimmune' response). For this reason these regulatory T cells have also been called 'Suppressor' T cells. These same self-tolerant cells are co-opted by cancer cells to prevent the recognition of, and an immune response against, tumour cells. All T cells originate from c-kit+Sca1+ haematopoietic stem cells (HSC) which reside in the bone marrow. In some cases the origin might be the fetal liver during embryonic development. The HSC then differentiate into multipotent progenitors (MPP) which retain the potential to become both myeloid and lymphoid cells. The process of differentiation then proceeds to a common lymphoid progenitor (CLP), which can only differentiate into T, B or NK cells. These CLP cells then migrate via the blood to the thymus, where they engraft. The earliest cells which arrived in the thymus are termed double-negative, as they express neither the CD4 nor CD8 co-receptor. The newly arrived CLP cells are CD4-CD8-CD44+CD25-ckit+ cells, and are termed early thymic progenitors (ETP) cells. These cells will then undergo a round of division and downregulate c-kit and are termed DN1 cells. At the DN2 stage (CD44+CD25+), cells upregulate the recombination genes RAG1 and RAG2 and re-arrange the TCRβ locus, combining V-D-J and constant region genes in an attempt to create a functional TCRβ chain. As the developing thymocyte progresses through to the DN3 stage (CD44-CD25+), T cell expresses an invariant α-chain called pre-Tα alongside the TCRβ gene. If the rearranged β-chain successfully pairs with the invariant α-chain, signals are produced which cease rearrangement of the β-chain (and silences the alternate allele). Although these signals require this pre-TCR at the cell surface, they are independent of ligand binding to the pre-TCR. If the pre-TCR forms, then the cell downregulates CD25 and is termed a DN4 cell (CD25-CD44-). These cells then undergo a round of proliferation and begin to re-arrange TCRα locus. After the TCRα locus has been re-arranged, the cell will express the full TCR on the surface and upregulate the co-receptor genes CD4 and CD8 and be termed 'double-positive' (DP) cells. These cells will then undergo positive selection, where T cells are selected to be capable of interacting with MHC. Positive selection involves the production of a signal by double-positive precursors that express either MHC Class I or II restricted receptors. DP cells selected on MHC class I will become CD8+ cells; DP cells selected on MHC class II will become CD4+ T cells. The cells then downregulate the non-selected co-receptor and become single-positive either CD4+ or CD8+ T cells (SP cells). The signal produced by these thymocytes result in RAG gene repression, long-term survival and migration into the medulla. The majority of cells in the thymus are DP cells, and the process of positive selection takes a number of days. Double-positive thymocytes (CD4+/CD8+) move deep into the thymic cortex, where they are presented with self-antigens. These self-antigens are expressed by thymic cortical epithelial cells on MHC molecules on the surface of cortical epithelial cells. Only those thymocytes that interact with MHC-I or MHC-II will receive a vital 'survival signal'. All that cannot (if they do not interact strongly enough) will die by 'death by neglect' (no survival signal). This process ensures that the selected T-cells will have an MHC affinity that can serve useful functions in the body (i.e., the cells must be able to interact with MHC and peptide complexes to effect immune responses). The vast majority of developing thymocytes will die during this process. A thymocyte's fate is determined during positive selection. Double-positive cells (CD4+/CD8+) that interact well with MHC class II molecules will eventually become CD4+ cells, whereas thymocytes that interact well with MHC class I molecules mature into CD8+ cells. A T cell becomes a CD4+ cell by down-regulating expression of its CD8 cell surface receptors. If the cell does not lose its signal, it will continue downregulating CD8 and become a CD4+, 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, which occurs in the thymic medulla (discussed below). Negative selection removes thymocytes that are capable of strongly binding with 'self' MHC peptides. Thymocytes that survive positive selection migrate towards the boundary of the cortex and medulla in the thymus. While in the medulla, they are again presented with a self-antigen presented on the MHC complex of medullary thymic epithelial cells (mTECs). mTECs must be AIRE+ to properly express self-antigens from all tissues of the body on their MHC class I peptides. Some mTECs are phagocytosed by thymic dendritic cells; this allows for presentation of self-antigens on MHC class II molecules (positively selected CD4+ cells must interact with MHC class II molecules, thus APCs, which possess MHC class II, must be present for CD4+ T-cell negative selection). Thymocytes that interact too strongly with the self-antigen receive an apoptotic signal that leads to cell death. However, some of these cells are selected to become Treg cells. The remaining cells exit the thymus as mature naïve T cells (also known as recent thymic emigrants). This process is an important component of central tolerance and serves to prevent the formation of self-reactive T cells that are capable of inducing autoimmune diseases in the host.

[ "Immune system", "Diabetes mellitus", "t cell cloning", "Mixed lymphocyte reaction", "T-Cell Immunodeficiency", "Jurkat cells", "Monoclonal Antibody OKT3" ]
Parent Topic
Child Topic
    No Parent Topic