T cell

T cells are a type of white blood cell that play a central role in cell-mediated immunity. The abbreviation "T" stands for thymus, the organ in which their final stage of development occurs. Although there are several different subsets of T cells, all of them express T cell receptor molecules on their surface.

• Cytotoxic T cells destroy virally infected cells and tumor cells, and are also implicated in transplant rejection. Also known as CD8⁺ T cells, since they express the CD8 glycoprotein at their surface.
• Helper T cells, or CD4⁺ T cells, are the "middlemen" of the immune response. Once activated, they divide rapidly and secrete cytokines that regulate or "help" the immune response. They are also a target of HIV infection, with the loss of CD4⁺ T cells leading to the symptoms of AIDS.
• Regulatory T cells, formerly known as suppressor T cells, are crucial for the maintenance of immunological tolerance. Mutations of the FOXP3 gene can prevent regulatory T cell development, causing the fatal autoimmune disease IPEX.

• Natural killer T cells

• γδ T cells

CD4 and CD8 refer to the characteristic glycoproteins on the surface of certain T cells. These CD molecules are convenient diagnostic markers for identifying T cells by flow cytometry.

==T cell development==U LIKE THAT COLM!! HUUH!! YEAH!! T cell precursors originate as pluripotent stem cells in the bone marrow, after which they populate the thymus as immature T cells or "thymocytes". These cells express neither CD4 nor CD8, and are therefore classed as double negative (CD4^-CD8^-) cells. As they progress through development they become double positive (CD4⁺CD8⁺), and finally single positive (CD4⁺CD8^- or CD4^-CD8⁺) cells. About 98% of thymocytes die in the thymus by failing either positive selection or negative selection, while the other 2% survive and leave the thymus to become mature T cells.

Positive selection

After populating the outer region of the thymus (cortex) as double negative thymocytes, double positive cells move deeper into the cortex where they are presented with antigens complexed with MHC molecules by cortical epithelial cells. Only those cells which bind the MHC/antigen complex with adequate affinity will receive a vital "survival signal". The other cells go into apoptosis and their remains are engulfed by macrophages. This process is called positive selection.

Negative selection

Cells that survive positive selection move towards the boundary of the thymic cortex and thymic medulla. In the medulla, they are again presented with antigen in complex with MHC molecules on the surface of medullary epithelial cells. If these antigens are recognized with high affinity, they die by apoptosis. This process is called negative selection - an important mechanism of immunological tolerance.

Hormonal substances (thymosin, interferon γ, interleukins, colony stimulating factors, thymopoetin, etc.) secreted by epithelial cells within the thymic (Hassal's) corpuscles promote the process of thymic education. Not only is the differentiation of T cells regulated by thymic epithelial cells, but T cells influence the architecture of the thymus itself.

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:

1. The interaction between TCR molecules and specific MHC/antigen complexes on APCs delivers signal 1 into the T cell.
2. 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).

External links

• [1], Immunobiology, 5th edition, Janeway, Charles A.; Travers, Paul; Walport, Mark; Shlomchik, Mark. New York and London: Garland Publishing; c2001.