Editing T cell (section)

===Conventional adaptive T cells===
====Helper CD4<sup>+</sup> T cells====
{{Main|T helper cell}}
[[File:CD4+ T cell subsets.pdf|thumb|Depiction of the various key subsets of CD4-positive T cells with corresponding associated cytokines and transcription factors.]]

[[T helper cell]]s (T<sub>H</sub> cells) assist other lymphocytes, including the maturation of [[B cell]]s into [[plasma cell]]s and [[memory B cell]]s, and activation of [[cytotoxic T cells]] and [[macrophage]]s. These cells are also known as '''CD4<sup>+</sup> T cells''' as they express the [[CD4]] glycoprotein on their surfaces. Helper T cells become activated when they are presented with [[peptide]] [[antigen]]s by [[MHC class II]] molecules, which are expressed on the surface of [[antigen-presenting cell]]s (APCs). Once activated, they divide rapidly and secrete [[cytokine]]s that regulate or assist the immune response. These cells can differentiate into one of several subtypes, which have different roles. Cytokines direct T cells into particular subtypes.<ref name="pmid17476341">{{cite journal|vauthors=Gutcher I, Becher B|title = APC-derived cytokines and T cell polarization in autoimmune inflammation|journal = J. Clin. Invest.|volume = 117|issue = 5|pages = 1119–27|year = 2007|pmid = 17476341|pmc = 1857272|doi = 10.1172/JCI31720}}</ref>

{|class="wikitable"
|+CD4<sup>+</sup> helper T cell subsets
!Cell type!!Cytokines Produced!!Key Transcription Factor!!Role in immune defense!!Related diseases
|-
|[[Th1 cell|Th1]]||[[IFNγ]], IL-2||[[TBX21|Tbet]]||Produce an inflammatory response, key for defense against intracellular bacteria, viruses and cancer.||MS, Type 1 diabetes
|-
|[[Th2]]||IL-4, IL-5, IL-13||GATA-3||Immunologically important against extracellular pathogens, such as worm infections||Asthma and other allergic diseases

|-
|[[Th17]]||IL-17F, IL-17A, IL-22||RORγt||Defense against gut pathogens and at mucosal barriers||MS, Rheumatoid Arthritis, Psoriasis
|-
|[[Th 9 cell|Th9]]<ref>{{cite journal|vauthors = Wang W, Sung N, Gilman-Sachs A, Kwak-Kim J|title = T Helper (Th) Cell Profiles in Pregnancy and Recurrent Pregnancy Losses: Th1/Th2/Th9/Th17/Th22/Tfh Cells|journal = Frontiers in Immunology|volume = 11|pages = 2025|date = 18 August 2020|pmid = 32973809|pmc = 7461801|doi = 10.3389/fimmu.2020.02025|doi-access = free}}</ref><ref name="Saravia 634–643">{{cite journal|vauthors = Saravia J, Chapman NM, Chi H|title = Helper T cell differentiation|journal = Cellular & Molecular Immunology|volume = 16|issue = 7|pages = 634–643|date = July 2019|pmid = 30867582|pmc = 6804569|doi = 10.1038/s41423-019-0220-6}}</ref>||IL-9||IRF4, PU.1||Defense against helminths (parasitic worms) and cell-dependent allergic inflammation||Multiple Sclerosis
|-

|[[Follicular B helper T cells|Tfh]]||IL-21, IL-4||Bcl-6||Help B cells produce antibodies||Asthma and other allergic diseases
|-
|Th22<ref>{{cite book|vauthors = Jia L, Wu C| title=T Helper Cell Differentiation and Their Function | chapter=The Biology and Functions of Th22 Cells | series=Advances in Experimental Medicine and Biology |volume = 841|pages = 209–230|year = 2014|pmid = 25261209|doi = 10.1007/978-94-017-9487-9_8|isbn = 978-94-017-9486-2}}</ref><ref name="Saravia 634–643"/>
|IL-22
|AHR
|Pathogenesis of allergic airway diseases and predominantly anti-inflammatory
|Crohn's Disease, Rheumatoid Arthritis, Tumors
|}

====Cytotoxic CD8+ T cells====
{{Main|Cytotoxic T cell}}
[[File:Killer T cells surround a cancer cell.png|thumb|Superresolution image of a group of cytotoxic T cells surrounding a cancer cell]]

[[Cytotoxic T cell]]s (T<sub>C</sub> cells, CTLs, T-killer cells, killer T cells) destroy virus-infected cells and tumor cells, and are also implicated in [[Organ transplant|transplant]] rejection. These cells are defined by the expression of the [[CD8]] protein on their cell surface. Cytotoxic T cells recognize their targets by binding to short peptides (8-11 [[amino acid]]s in length) associated with [[MHC class I]] molecules, present on the surface of all nucleated cells. Cytotoxic T cells also produce the key cytokines IL-2 and IFNγ. These cytokines influence the effector functions of other cells, in particular macrophages and NK cells.

====Memory T cells====
{{Main|Memory T cell}}
Antigen-naive T cells expand and differentiate into memory and [[effector T cells]] after they encounter their cognate antigen within the context of an MHC molecule on the surface of a professional antigen presenting cell (e.g. a dendritic cell). Appropriate co-stimulation must be present at the time of antigen encounter for this process to occur. Historically, memory T cells were thought to belong to either the effector or central memory subtypes, each with their own distinguishing set of cell surface markers (see below).<ref>{{cite journal|vauthors= Sallusto F, Lenig D, Förster R, Lipp M, Lanzavecchia A|title = Two subsets of memory T lymphocytes with distinct homing potentials and effector functions.|journal = Nature|volume = 401|issue = 6754|pages = 708–712|year = 1999|pmid = 10537110|doi = 10.1038/44385|bibcode = 1999Natur.401..708S|s2cid = 4378970}}</ref> Subsequently, numerous new populations of memory T cells were discovered including tissue-resident memory T (Trm) cells, stem memory TSCM cells, and virtual memory T cells. The single unifying theme for all [[memory T cell]] subtypes is that they are long-lived and can quickly expand to large numbers of effector T cells upon re-exposure to their cognate antigen. By this mechanism they provide the immune system with "memory" against previously encountered pathogens. Memory T cells may be either CD4<sup>+</sup> or CD8<sup>+</sup> and usually express [[CD45|CD45RO]].<ref name="pmid2965180">{{cite journal|vauthors=Akbar AN, Terry L, Timms A, Beverley PC, Janossy G|title = Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells|journal = J. Immunol.|volume = 140|issue = 7|pages = 2171–8|date = April 1988|doi = 10.4049/jimmunol.140.7.2171|pmid = 2965180|s2cid = 22340282|doi-access = free}}</ref>

Memory T cell subtypes:
*Central memory T cells (T<sub>CM</sub> cells) express CD45RO, [[C-C chemokine receptor type 7]] (CCR7), and [[L-selectin]] (CD62L). Central memory T cells also have intermediate to high expression of [[CD44]]. This memory subpopulation is commonly found in the [[lymph node]]s and in the peripheral circulation. (Note- CD44 expression is usually used to distinguish murine naive from memory T cells).
*Effector memory T cells (T<sub>EM</sub> cells and T<sub>EMRA</sub> cells) express CD45RO but lack expression of CCR7 and [[L-selectin]]. They also have intermediate to high expression of [[CD44]]. These memory T cells lack lymph node-homing receptors and are thus found in the peripheral circulation and tissues.<ref>{{cite journal|vauthors=Willinger T, Freeman T, Hasegawa H, McMichael AJ, Callan MF|title = Molecular signatures distinguish human central memory from effector memory CD8 T cell subsets.|journal = Journal of Immunology|volume = 175|issue = 9|pages = 5895–903|year = 2005|pmid = 16237082|doi = 10.4049/jimmunol.175.9.5895|s2cid = 16412760|url = https://www.pure.ed.ac.uk/ws/files/13962949/Molecular_Signatures_Distinguish_Human_Central_Memory_from_Effector.pdf|doi-access = free}}</ref> T<sub>EMRA</sub> stands for terminally differentiated effector memory cells re-expressing CD45RA, which is a marker usually found on naive T cells.<ref>{{cite journal|vauthors= Koch S, Larbi A, Derhovanessian E, Özcelik D, Naumova E, Pawelec G|title = Multiparameter flow cytometric analysis of CD4 and CD8 T cell subsets in young and old people.|journal = Immunity & Ageing|volume = 5|issue = 6|pages = 6|year = 2008|pmid = 18657274|doi = 10.1186/1742-4933-5-6|pmc=2515281 | doi-access=free }}</ref>
*[[Tissue-resident memory T cells]] (T<sub>RM</sub>) occupy tissues (skin, lung, etc.) without recirculating. One cell surface marker that has been associated with T<sub>RM</sub> is the intern αeβ7, also known as CD103.<ref>{{cite journal|vauthors = Shin H, Iwasaki A|title = Tissue-resident memory T cells|journal = Immunological Reviews|volume = 255|issue = 1|pages = 165–81|date = September 2013|pmid = 23947354|pmc = 3748618|doi = 10.1111/imr.12087}}</ref>
*[[Virtual memory T cells]] (T<sub>VM</sub>) differ from the other memory subsets in that they do not originate following a strong clonal expansion event. Thus, although this population as a whole is abundant within the peripheral circulation, individual virtual memory T cell clones reside at relatively low frequencies. One theory is that homeostatic proliferation gives rise to this T cell population. Although CD8 virtual memory T cells were the first to be described,<ref>{{cite journal|vauthors=Lee YJ, Jameson SC, Hogquist KA|title = Alternative memory in the CD8 T cell lineage.|journal = Trends in Immunology|volume = 32|issue = 2|pages = 50–56|year = 2011|pmid = 21288770|doi = 10.1016/j.it.2010.12.004|pmc=3039080}}</ref> it is now known that CD4 virtual memory cells also exist.<ref>{{cite journal|vauthors= Marusina AI, Ono Y, Merleev AA, Shimoda M, Ogawa H, Wang EA, Kondo K, Olney L, Luxardi G, Miyamura Y, Yilma TD, Villalobos IB, Bergstrom JW, Kronenberg DG, Soulika AM, Adamopoulos IE, Maverakis E|title = CD4<sup>+</sup> virtual memory: Antigen-inexperienced T cells reside in the naïve, regulatory, and memory T cell compartments at similar frequencies, implications for autoimmunity.|journal = Journal of Autoimmunity|volume = 77|pages = 76–88|year = 2017|pmid = 27894837|pmc = 6066671|doi = 10.1016/j.jaut.2016.11.001}}</ref>

====Regulatory CD4<sup>+</sup> T cells====
{{Main|Regulatory T cell}}

[[Regulatory T cell]]s are crucial for the maintenance of [[immunological tolerance]]. Their major role is to shut down T cell–mediated immunity toward the end of an immune reaction and to suppress [[autoreactive T cell]]s that escaped the process of negative selection in the thymus.

Two major classes of CD4<sup>+</sup> T<sub>reg</sub> cells have been described—FOXP3<sup>+</sup> T<sub>reg</sub> cells and FOXP3<sup>−</sup> T<sub>reg</sub> cells.

Regulatory T cells can develop either during normal development in the thymus, and are then known as thymic Treg cells, or can be induced peripherally and are called peripherally derived Treg cells. These two subsets were previously called "naturally occurring" and "adaptive" (or "induced"), respectively.<ref name="pmid23507634">{{cite journal|vauthors=Abbas AK, Benoist C, Bluestone JA, Campbell DJ, Ghosh S, Hori S, Jiang S, Kuchroo VK, Mathis D, Roncarolo MG, Rudensky A, Sakaguchi S, Shevach EM, Vignali DA, Ziegler SF|title=Regulatory T cells: recommendations to simplify the nomenclature|journal=Nat. Immunol.|volume=14|issue=4|pages=307–8|year=2013|pmid=23507634|doi=10.1038/ni.2554|s2cid=11294516|url=http://www.escholarship.org/uc/item/75m8c11s|doi-access=free}}</ref> Both subsets require the expression of the [[transcription factor]] [[FOXP3]] which can be used to identify the cells. Mutations of the ''FOXP3'' gene can prevent regulatory T cell development, causing the fatal [[autoimmune disease]] [[IPEX (syndrome)|IPEX]].

Several other types of T cells have suppressive activity, but do not express FOXP3 constitutively. These include [[Type 1 regulatory T cell|Tr1]] and [[T helper 3 cell|Th3]] cells, which are thought to originate during an immune response and act by producing suppressive molecules. Tr1 cells are associated with IL-10, and Th3 cells are associated with [[TGF-beta]]. Recently, [[Th17 cells]] have been added to this list.<ref name="pmid24434314">{{cite journal|vauthors=Singh B, Schwartz JA, Sandrock C, Bellemore SM, Nikoopour E|title=Modulation of autoimmune diseases by interleukin (IL)-17 producing regulatory T helper (Th17) cells|journal=Indian J. Med. Res.|volume=138|issue=5|pages=591–4|year=2013|pmid=24434314|pmc=3928692}}</ref>