Editing Thymus (section)

== Function ==
[[File:Intrathymic T Cell Differentiation.JPG|right|frameless]]

===T cell maturation===
The thymus facilitates the maturation of [[T cell]]s, an important part of the [[immune system]] providing [[cell-mediated immunity]].<ref name=GH2016>{{cite book |last1=Hall |first1=John E. | name-list-style = vanc |title=Guyton and Hall textbook of medical physiology |year=2016 |publisher=Elsevier |location=Philadelphia |isbn=978-1-4557-7016-8 |edition=13th|pages=466–7}}</ref> T cells begin as hematopoietic precursors from the bone-marrow, and migrate to the thymus, where they are referred to as [[thymocyte]]s. In the thymus, they undergo a process of maturation, which involves ensuring the cells react against [[antigen]]s ("positive selection"), but that they do not react against antigens found on body tissue ("negative selection").<ref name=GH2016 /> Once mature, T cells emigrate from the thymus to provide vital functions in the immune system.<ref name=GH2016 /><ref name="Robbins9thC6" />

Each T cell has a distinct [[T cell receptor]], suited to a specific substance, called an [[antigen]].<ref name="Robbins9thC6">{{cite book |title=Robbins and Cotran Pathologic Basis of Disease |isbn=9780323296397 |edition=9th (online)|section=Chapter 6. Diseases of the immune system. The normal immune system.|last1=Kumar |first1=Vinay |last2=Abbas |first2=Abul K. |last3=Fausto |first3=Nelson |last4=Aster |first4=Jon C. | name-list-style = vanc |date=2014-08-27 |publisher=Elsevier Health Sciences }}</ref> Most T cell receptors bind to the [[major histocompatibility complex]] on cells of the body. The MHC presents an antigen to the T cell receptor, which becomes active if this matches the specific T cell receptor.<ref name="Robbins9thC6" /> In order to be properly functional, a mature T cell needs to be able to bind to the MHC molecule ("positive selection"), and not to react against antigens that are actually from the tissues of body ("negative selection").<ref name="Robbins9thC6" /> Positive selection occurs in the cortex and negative selection occurs in the medulla of the thymus.<ref name="MDB2019" /> After this process T cells that have survived leave the thymus, regulated by [[sphingosine-1-phosphate]].<ref name="MDB2019" /> Further maturation occurs in the peripheral circulation.<ref name="MDB2019" /> Some of this is because of hormones and [[cytokine]]s secreted by cells within the thymus, including [[thymulin]], [[thymopoietin]], and [[thymosin]]s.<ref name="Wheaters2013" />

===Positive selection===
T cells have distinct T cell receptors. These distinct receptors are formed by process of [[V(D)J recombination]] gene rearrangement stimulated by [[RAG1]] and [[RAG2]] genes.<ref name="MDB2019">{{cite book|last1=Hohl|first1=Tobias M.| veditors = Bennett JE, Dolin R, Blaser MJ |title=Mandell, Douglas, and Bennett's principles and practice of infectious diseases|date=2019|publisher=Elsevier|isbn=9780323482554|edition=9th (online)|chapter=6. Cell mediated defence against infection: Thymic selection of CD4+ and CD8+ T Cells}}</ref> This process is error-prone, and some thymocytes fail to make functional T-cell receptors, whereas other thymocytes make T-cell receptors that are autoreactive.<ref name=":0" /> If a functional T cell receptor is formed, the thymocyte will begin to express simultaneously the cell surface proteins [[CD4]] and [[CD8]].<ref name="MDB2019" />

The survival and nature of the T cell then depends on its interaction with surrounding thymic epithelial cells. Here, the T cell receptor interacts with the MHC molecules on the surface of epithelial cells.<ref name="MDB2019" /> A T cell with a receptor that doesn't react, or reacts weakly, will die by [[apoptosis]]. A T cell that does react will survive and proliferate.<ref name="MDB2019" /> A mature T cell expresses only CD4 or CD8, but not both.<ref name="Robbins9thC6" /> This depends on the strength of binding between the TCR and MHC class 1 or class 2.<ref name="MDB2019" /> A T cell receptor that binds mostly to MHC class I tends to produce a mature "cytotoxic" CD8 positive T cell; a T cell receptor that binds mostly to MHC class II tends to produce a CD4 positive T cell.<ref name=":0" />

===Negative selection===
T cells that attack the body's own proteins are eliminated in the thymus, called "negative selection".<ref name="Robbins9thC6" /> Epithelial cells in the medulla and dendritic cells in the thymus express major proteins from elsewhere in the body.<ref name="MDB2019" /> The gene that stimulates this is [[AIRE]].<ref name="Robbins9thC6" /><ref name="MDB2019" />  Thymocytes that react strongly to self antigens do not survive, and die by apoptosis.<ref name="Robbins9thC6" /><ref name="MDB2019" /> Some CD4 positive T cells exposed to self antigens persist as [[T regulatory cell]]s.<ref name="Robbins9thC6" />