T cell

T cells are a subset of lymphocytes that play a large role in the immune response. The abbreviation "T" stands for thymus, the organ in which their final stage of development occurs.

• Cytotoxic T cells (CD8⁺) destroy infected cells. These cells function as "killer" or cytotoxic cells because they are able to destroy target cells which express specific antigens that they recognize.
• Helper T cells (CD4⁺) are "middlemen" in the immune response. When they get activated, they proliferate and secrete cytokines that regulate or "help" effector lymphocyte function. They are known as one of the targets of HIV infection, and the decrease of CD4⁺ T cells results in AIDS. Some helper T cells secrete cytokines that turn off the immune response once an antigen has been eliminated from the body.
• Regulatory T cells (also known as suppressor T cells) suppress activation of the immune system and maintain immune system homeostasis. Failure of regulatory T cells to function properly may result in autoimmune diseases in which the immunocytes attack healthy cells in the body.

Every effective immune response involves T cell activation; however, T cells are especially important in cell-mediated immunity, which is the defense against tumor cells and pathogenic organisms inside body cells. They are also involved in rejection reactions.

CD4 and CD8 refer to the characteristic antigens on the surface of the different sub-types of T-lymphocytes. These CD molecules (or Clusters of Differentiation) are convenient diagnostic markers for identifying and quantitating these cells by flow cytometry using specific antibodies against them. T cell activity and secretions are frequently determined using the ELISPOT technique.

T cell development

Throughout life, a source of all lymphocytes remains bone marrow. Progeny of multipotential lymphoid stem cells (CFU-L) that are destined to become T cells, move into thymus, where they are called thymocytes.

Thymocytes are immature T cells. The process of differentiation called thymic education occurs in a few stages in the subcapsular region of the thymic cortex. At first, multipotential T cells move to the edge of the thymic cortex. These cells express CD2,CD7 and CD3, but neither CD4 nor CD8 (i.e. they are double negative, CD4^-CD8^- cells). In the early stage of differentiation, they start to express CD2 and CD7 molecules. This is followed by expression of the CD1 molecule, that marks the midstage of T cell differentiation. At the end of differentiation they express T cell receptors, CD3, CD4 and CD8 molecules. Because they have both CD4 and CD8 molecules at their surface, they are said to be double positive (CD4⁺CD8⁺).

Double positive cells move deeper in the cortex where they are presented with self and foreign antigens complexed with class I and class II MHC molecules by type II and type III cortical epithelioreticular cells. Only those cells that recognize the antigen presented and bind the MHC molecule with affinity high enough, survive. Other cells go into apoptosis and their remains are engulfed by macrophages. This process is called positive selection.

All their life T cells recognize only those antigens, for which they are specific and that are binded in a complex with the MHC molecule of the type they were presented with in the thymic cortex. They are said to be limited with type I or type II MHC molecules.

The cells that survive positive selection move towards the thymic medulla where at the boundary between thymic cortex and thymic medulla and in the medulla, they get are presented with self-antigens in a complex with MHC molecules on the surface of type V and VI thymic epithelioreticular cells. If they do recognize these antigens, they die by apoptosis. Only those cells survive that do not recognize them. Other T cells die by apoptosis (a small fraction actually survives but normally is controlled so it does not cause autoimmune diseases). This process is called negative selection.

T cells go into apoptosis if they cannot express their TCR receptors, if they aren't positively selected, or if they are removed by negative selection. About 98% of T cells die in the thymus. Their remains get engulfed by macrophages. The other 2% of T cells are selected to survive and mature. These cells lose either their CD4 molecules or CD8 molecules and leave the thymus via postcapillary venules.

Hormonal substances (thymosin, interferon γ, interleukins, colony stimulating factors, thymopoetin, etc.) secreted by type VI epithelioreticular cells within the thymic (Hassal's) corpuscles promote the process of thymic education.

Not only is the differentiation of T cells regulated by thymic epithelioreticular cells, but T cells also influence the microarchitecture of thymic epithelioreticular cells. This bi-directionality is called "cross-talk".

References

• Janeway, et al., Immunobiology. 6th ed., Garland Science, 2005. ISBN 0815341016. NCBI makes the 5th edition available electronically at [1] (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=imm.TOC&depth=10).
• Michael H. Ross, et al. Histology: A Text and Atlas, 4th ed., Lippincott Williams & Wilkins, 2003, ISBN 0683302426
• Marjan Vozelj, Temelji imunologije, 1th ed., DZS, 2005, Ljubljana, Slovenia, ISBN 8634128636

External links

• PLOS Primer: Antigen-Specific T Cells: Analyses of the Needles in the Haystack (http://www.plosbiology.org/plosonline/?request=get-document&doi=10.1371%2Fjournal.pbio.0000078)
• T Cell Workshop (http://www.idsoc.org/Octworkshop.html), Research by the Immunology of Diabetes Society

Immune system

Humoral immune system - Cellular immune system - Lymphatic system

White blood cells - B cells - Antibodies - Antigen (MHC)

Lymphocytes: T cells (Cytotoxic & Helper) - B cells (Plasma cells & Memory B cells)

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