Meta tags:
Headings (most frequently used words):
cells, development, cell, tcr, selection, during, and, cancer, cd4, contents, types, of, activation, clinical, significance, see, also, references, further, reading, origin, early, migration, to, the, thymus, thymic, output, conventional, adaptive, innate, like, antigen, discrimination, deficiency, exhaustion, chain, positive, negative, summary, helper, cytotoxic, cd8, memory, regulatory, natural, killer, mucosal, associated, invariant, gamma, delta, chronic, infection, sepsis, transplantation,
Text of the page (most frequently used words):
cells (306), the (302), and (238), cell (196), are (87), pmid (80), doi (79), pmc (51), immune (50), that (50), cd8 (48), #memory (46), cd4 (45), with (40), for (38), also (38), exhaustion (37), can (37), edit (35), which (34), #antigen (33), mhc (32), these (32), selection (29), this (28), immunology (27), their (27), from (26), associated (26), during (26), activation (26), they (25), molecules (24), cancer (23), positive (23), tcr (23), thymus (21), response (20), invariant (20), infection (20), expression (20), helper (19), system (18), killer (18), regulatory (18), cytotoxic (18), self (18), have (18), journal (17), negative (17), receptor (17), surface (17), then (17), thymocytes (17), other (16), mucosal (16), s2cid (16), role (16), class (15), 1038 (15), 1016 (15), not (15), development (15), immunity (14), innate (14), after (14), thymic (14), main (14), into (14), may (13), cytokines (13), 2015 (13), transplantation (13), known (13), proteins (13), process (13), activated (12), like (12), diseases (12), 2011 (12), function (12), sepsis (12), 2014 (12), effector (12), subsets (12), will (12), chain (12), antigens (11), science (11), 2018 (11), nature (11), functional (11), receptors (11), some (11), article (11), presented (11), tolerance (10), adaptive (10), natural (10), reg (10), clinical (10), specific (10), van (10), signal (10), functions (10), express (10), one (10), both (10), become (10), major (10), against (10), human (9), lymphocytes (9), pdf (9), bibcode (9), blood (9), 2016 (9), tumor (9), chronic (9), immunol (9), mait (9), produce (9), protein (9), such (9), but (9), types (9), central (8), complex (8), stem (8), thymocyte (8), 2003 (8), leukemia (8), virus (8), infected (8), differentiation (8), viral (8), pathogens (8), lymphoma (8), autoimmune (8), two (8), exposure (8), its (8), has (8), able (8), been (8), naive (8), recognize (8), must (8), double (8), wikipedia (7), was (7), peripheral (7), lymphoid (7), 978 (7), liu (7), 2012 (7), november (7), inhibitory (7), biology (7), mediated (7), alpha (7), peptide (7), responses (7), 2010 (7), when (7), molecular (7), peptides (7), mr1 (7), mature (7), called (7), important (7), membrane (7), produced (7), interact (7), usually (7), binding (7), cd44 (7), subtypes (7), toggle (6), february (6), all (6), states (6), national (6), stimulation (6), autoimmunity (6), type (6), induced (6), pre (6), september (6), june (6), isbn (6), july (6), multiple (6), 2017 (6), 1111 (6), august (6), december (6), death (6), beta (6), signaling (6), recognition (6), inflammatory (6), virtual (6), develop (6), well (6), play (6), several (6), gene (6), first (6), create (6), transcription (6), expressed (6), cd25 (6), found (6), about (5), page (5), different (5), retrieved (5), deletion (5), antibodies (5), apcs (5), new (5), garland (5), disease (5), further (5), via (5), chang (5), restricted (5), acute (5), march (5), 1186 (5), research (5), der (5), liver (5), critical (5), yang (5), medicine (5), reviews (5), factor (5), loss (5), required (5), 3389 (5), fimmu (5), april (5), 2021 (5), discrimination (5), 2007 (5), allergic (5), apc (5), derived (5), lymphocyte (5), see (5), many (5), now (5), while (5), there (5), infections (5), including (5), high (5), stage (5), leads (5), exhausted (5), typically (5), present (5), same (5), only (5), syndrome (5), termed (5), deficiency (5), although (5), most (5), calcium (5), cd28 (5), signalling (5), becomes (5), presenting (5), population (5), foxp3 (5), either (5), were (5), developing (5), contents (4), search (4), use (4), united (4), cellular (4), clonal (4), affinity (4), inflammation (4), dendritic (4), presentation (4), hematopoietic (4), cytokine (4), 2009 (4), 2001 (4), sciences (4), checkpoint (4), wang (4), 106 (4), marrow (4), hdl (4), 2008 (4), graft (4), rejection (4), transplant (4), anti (4), die (4), experimental (4), 2013 (4), immunological (4), causes (4), respond (4), help (4), frontiers (4), unconventional (4), th17 (4), reside (4), tissue (4), distinct (4), epithelial (4), migration (4), shown (4), changes (4), number (4), factors (4), least (4), ability (4), large (4), common (4), include (4), healthy (4), pmhc (4), contain (4), plc (4), activates (4), does (4), pathway (4), where (4), activate (4), genes (4), chains (4), tcrβ (4), stimulatory (4), mechanism (4), once (4), variety (4), marker (4), prevent (4), molecule (4), occurs (4), histocompatibility (4), production (4), phosphoantigens (4), gamma (4), delta (4), capable (4), conventional (4), differentiate (4), key (4), defense (4), undergo (4), medulla (4), strongly (4), migrate (4), random (4), hide (4), move (4), sidebar (4), subsection (4), view (3), additional (3), terms (3), site (3), commons (3), articles (3), short (3), wikidata (3), data (3), control (3), recombination (3), maturation (3), pregnancy (3), depletion (3), anergy (3), reactivity (3), professional (3), antigenic (3), naïve (3), plasma (3), janeway (3), 8153 (3), immunobiology (3), health (3), 1073 (3), pnas (3), proceedings (3), academy (3), america (3), dysfunctional (3), blockade (3), zhang (3), tim (3), relapse (3), patients (3), characterized (3), activity (3), clim (3), 009 (3), induce (3), regulate (3), williams (3), hansen (3), xia (3), late (3), 4049 (3), jimmunol (3), jones (3), society (3), osborne (3), hotchkiss (3), survival (3), 2006 (3), 1128 (3), potential (3), dysfunction (3), more (3), reactive (3), kim (3), patel (3), maintenance (3), expansion (3), 1146 (3), annurev (3), godfrey (3), rossjohn (3), mccluskey (3), vitamin (3), sclerosis (3), 2171 (3), murine (3), roles (3), resident (3), distinguish (3), homing (3), th22 (3), bone (3), recent (3), distinguished (3), name (3), information (3), gut (3), studies (3), them (3), following (3), presence (3), over (3), time (3), long (3), term (3), conditions (3), lack (3), needed (3), tgf (3), furthermore (3), encounter (3), body (3), combined (3), defined (3), approach (3), primarily (3), defines (3), second (3), markers (3), cases (3), deficiencies (3), significance (3), unique (3), subset (3), however (3), pathogen (3), space (3), dependent (3), described (3), dag (3), pkc (3), phosphorylates (3), domains (3), bind (3), binds (3), rather (3), recruit (3), allowing (3), nfat (3), allows (3), phosphorylated (3), active (3), pi3k (3), activating (3), rapidly (3), turn (3), set (3), proliferation (3), independent (3), total (3), tcrα (3), small (3), respectively (3), upon (3), cognate (3), mhcii (3), macrophages (3), amino (3), acids (3), length (3), through (3), within (3), ipp (3), dmapp (3), corresponding (3), secrete (3), thought (3), arthritis (3), nkt (3), unlike (3), context (3), originate (3), thus (3), circulation (3), cd45ro (3), each (3), single (3), selected (3), successfully (3), locus (3), cortex (3), mtecs (3), receive (3), attempt (3), clp (3), early (3), origin (3), tools (3), languages (2), table (2), contact (2), privacy (2), policy (2), non (2), wikimedia (2), last (2), 2026 (2), categories (2), unsourced (2), statements (2), description (2), international (2), hla (2), diversity (2), immunodeficiency (2), allergy (2), action (2), polyclonal (2), antibody (2), variation (2), complement (2), archived (2), original (2), infectious (2), reading (2), weiss (2), 108 (2), medical (2), kong (2), approved (2), zhu (2), predict (2), allogeneic (2), huang (2), channel (2), target (2), 105 (2), 018 (2), protect (2), display (2), vignali (2), recipient (2), successful (2), transfer (2), shi (2), mare (2), bredemeijer (2), gent (2), mancham (2), laan (2), jonge (2), metselaar (2), kwekkeboom (2), 1765 (2), american (2), primary (2), hyporesponsiveness (2), fewer (2), lang (2), induces (2), alloantigen (2), alloreactive (2), acceptance (2), kidney (2), series (2), biological (2), defects (2), jama (2), increased (2), freeman (2), rudensky (2), ahmed (2), 1084 (2), jem (2), between (2), imr (2), 255 (2), immuni (2), 015 (2), persistence (2), vivo (2), interleukin (2), wherry (2), jvi (2), virology (2), progressive (2), 1994 (2), 8056 (2), environment (2), liston (2), garg (2), 2025 (2), s41577 (2), 1126 (2), held (2), 2019 (2), 019 (2), how (2), make (2), operational (2), lymphomas (2), disorders (2), 002 (2), trends (2), germain (2), 619 (2), understanding (2), ligand (2), october (2), oxygen (2), species (2), spacex (2), crs (2), 117 (2), ctls (2), targets (2), traf6 (2), bridge (2), maverakis (2), shimoda (2), jaut (2), theory (2), treatment (2), 1999 (2), bevan (2), generating (2), 300 (2), 421 (2), annual (2), review (2), corbett (2), chen (2), hair (2), fairlie (2), 491 (2), microbial (2), metabolites (2), bacteria (2), lantz (2), 176 (2), bowel (2), keller (2), precursors (2), gold (2), lewinsohn (2), microbes (2), 6633824 (2), 1155 (2), producing (2), kondo (2), similar (2), frequencies (2), jameson (2), hogquist (2), alternative (2), flow (2), people (2), 175 (2), 5895 (2), 140 (2), feature (2), 401 (2), 017 (2), 2020 (2), profiles (2), th1 (2), th2 (2), th9 (2), tfh (2), 1172 (2), hiv (2), 529 (2), murphy (2), kenneth (2), 8th (2), 4243 (2), jci (2), insight (2), emigrants (2), medullary (2), foreign (2), patterns (2), mice (2), 925135 (2), alberts (2), johnson (2), lewis (2), raff (2), roberts (2), walter (2), 2002 (2), 4th (2), derive (2), references (2), immunosenescence (2), plays (2), based (2), therapies (2), targeted (2), those (2), vital (2), persistent (2), effect (2), beneficial (2), carries (2), longer (2), higher (2), load (2), increases (2), another (2), pd1 (2), trigger (2), therefore (2), occur (2), result (2), initial (2), pro (2), apoptotic (2), ctla (2), programmed (2), lose (2), eventually (2), even (2), cd62l (2), cd69 (2), three (2), absence (2), cause (2), might (2), tolerization (2), recently (2), forms (2), severe (2), herpes (2), intracellular (2), individual (2), complete (2), hereditary (2), cancerous (2), initiate (2), pathways (2), example (2), causing (2), cytosolic (2), form (2), degradation (2), serves (2), ubiquitination (2), nucleus (2), slp (2), potentially (2), trisphosphate (2), pip3 (2), release (2), cytosol (2), low (2), extracellular (2), calcineurin (2), ip3 (2), lat (2), cd3ζ (2), motifs (2), itam (2), lck (2), zap (2), comes (2), relatively (2), products (2), constitutively (2), constitute (2), icos (2), without (2), prevents (2), regulated (2), essential (2), contribute (2), direct (2), directly (2), represent (2), possess (2), than (2), majority (2), group (2), humans (2), mostly (2), still (2), whole (2), vγ9 (2), vδ2 (2), named (2), addition (2), upregulate (2), pyrophosphate (2), mucosa (2), bacterially (2), yet (2), viruses (2), populations (2), being (2), suppressive (2), tr1 (2), th3 (2), peripherally (2), previously (2), require (2), used (2), identify (2), down (2), tissues (2), ccr7 (2), intermediate (2), lymph (2), differentiated (2), emra (2), selectin (2), commonly (2), expand (2), appropriate (2), own (2), provide (2), encountered (2), ifnγ (2), particular (2), rheumatoid (2), asthma (2), related (2), assist (2), processes (2), whereas (2), survive (2), leave (2), output (2), continue (2), rearranged (2), too (2), citation (2), summary (2), aire (2), makes (2), cortical (2), arrange (2), signals (2), round (2), due (2), threats (2), stages (2), arrived (2), progenitor (2), kit (2), hsc (2), left (2), appearance (2), upload (2), file (2), links (2), history (2), read (2), english (2), bahasa (2), log (2), account (2), donate (2), menu (2), add, topic, mobile, cookie, statement, statistics, developers, code, conduct, legal, safety, contacts, disclaimers, text, available, under, apply, using, you, agree, registered, trademark, profit, organization, foundation, inc, creative, attribution, sharealike, license, edited, utc, hidden, https, org, index, php, title, t_cell, oldid, 1356316901, yale, lux, israel, spain, czech, republic, bnf, france, gnd, authority, databases, cytolysin, opsonin, substances, humoral, immunoglobulin, switching, junctional, somatic, hypermutation, immunogenetics, privilege, inaction, cross, hypersensitivity, alloimmunity, paratope, idiotype, isotype, allotype, microantibody, autoantibody, monoclonal, immunogen, macrophage, mimotope, conformational, linear, epitope, hapten, allergen, superantigen, lymphocytic, category, prolymphocyte, lymphoblast, lymphopoiesis, lti, nuocytes, uterine, null, lymphokine, lymphoplasmacytoid, transitional, b10, marginal, zone, follicular, plasmablast, institute, travers, walport, shlomchik, 5th, york, 3642, bhadra, gigley, khan, 9201, 21576466, 3107287, 1015298108, 2011pnas, 9196b, 9196, toxoplasma, reactivation, rescue, pdl, writer, agency, 香港醫學作家, medipr, medipaper, hong, fda, inhibitors, immunotherapies, claxton, ehmann, rybka, e330, 26230954, 4526784, bcj, associate, aml, post, compromised, associates, lymphoblastic, 29477343, 190, conforti, ion, network, immunotherapy, 22189042, 142, lakins, ghorani, munir, martins, shields, 948, 29507342, 5838096, s41467, 03347, 2018natco, 948l, communications, fibroblasts, tumour, zelle, rieser, thangavadivel, biedermann, brunner, stoitzner, willenbacher, 116, 27809856, 5093947, s13045, 016, 0345, hematology, oncology, myeloma, features, senescence, woo, turnis, goldberg, bankoti, selby, nirschl, bettini, gravano, vogel, tangsombatvisit, grosso, netto, smeltzer, chaux, utz, workman, pardoll, korman, drake, 22186141, 3288154, 1158, 0008, 5472, 1620, 917, lag, synergistically, promote, tumoral, escape, cooley, bachanova, blazar, weisdorf, miller, verneris, 622, 29197679, 5826878, bbmt, 022, 618, adoptive, haploidentical, tapirdamaz, campenhout, litjens, betjes, eijk, 5348557, 25943855, 91951, ajt, 13288, 2431, cmv, donor, rejections, gassa, jian, kalkavan, duhan, honke, shaabani, friedrich, dolff, wahlers, kribben, hardt, witzke, 26963287, 1159, 000443067, 1171, physiology, biochemistry, hearts, heide, mulder, boer, heemskerk, 26170387, 91857, 1500440, 1838, 195, cytomegalovirus, cd244, steger, denecke, sawitzki, karim, wood, 33409478, 18475193, 1097, 0b013e31816dd64a, 1339, exhaustive, determination, halloran, famulski, hidalgo, salazar, merino, lopez, matas, picton, freitas, bromberg, serón, sellarés, einecke, reeve, 25377077, 4483591, 1681, asn, 2014060588, 1711, nephrology, disappearance, despite, continued, recipients, wells, strom, turka, 1409, 11375065, 1088449, 1098, rstb, 0845, 617, 356, philosophical, transactions, royal, london, wei, yao, deng, xie, tang, lactose, reverses, injury, apoptosis, 21657071, 29689313, 010, 192, patera, drewry, beiter, 1254, 27671246, 5110001, 1189, jlb, 4hi0616, 255r, 1239, 100, leukocyte, frontline, restored, targeting, shindo, mcdonough, ramachandra, sasikumar, 27993215, 5535083, jss, 099, 208, surgical, improves, boomer, takasu, walton, bricker, jarman, kreisel, krupnick, srivastava, swanson, green, 605, 22187279, 3361243, 1001, 1829, 2594, 306, immunosuppression, who, organ, failure, otto, sossdorf, claus, rödel, menge, reinhart, bauer, riedemann, r183, 21798063, 3387626, cc10332, care, phase, microbiological, burden, rate, penaloza, macmaster, kamphorst, wieland, araki, iyer, west, mara, konieczny, sharpe, 25113973, 4144726, 20132577, 1905, 211, interplay, modulating, lcmv, veiga, parga, sehrawat, rouse, 23947355, 3748387, 12085, 182, tinoco, alcalde, sauer, zuniga, 19604493, 3039716, 145, intrinsic, transforming, growth, mediates, brooks, trifilo, edelmann, teyton, mcgavern, 17041596, 2535582, nm1492, 1301, determines, clearance, oldstone, okagawa, konnai, nishimori, maekawa, goto, ikebuchi, kohara, suzuki, yamada, kato, murata, ohashi, 29914540, 6006750, s13567, 0543, veterinary, bovine, 11052693, 21739672, 2035, 492, angelosanto, blackburn, crawford, 22623779, 3421680, 00889, 8161, commitment, matloubian, concepcion, 7966595, 237269, 8063, sustain, pan, luo, feng, dittmer, 219, 29483916, 5816053, 00219, front, hepatitis, maintain, reexposure, cox, zajac, 20201977, 2842494, 1365, 2567, 03255, 474, 129, characteristics, conversion, galluzzi, smith, 679, 40216888, 025, 01161, 662, naulaerts, datsi, borras, antoranz, martinez, messiaen, vanmeerbeek, sprooten, laureano, govaerts, panovska, derweduwe, sabel, rapp, mackay, herck, gelens, venken, bechter, bergers, vleeschouwer, den, eynde, lambrechts, verfaillie, bosisio, tejpar, borst, sorg, smet, 2023, multiomics, spatial, mapping, characterizes, 691, eadd1016, 37043555, 2078, 278089, scitranslmed, add1016, translational, blank, haining, hogan, kallies, lugli, 674, 31570879, 7286441, 0221, 2019natri, 665b, 665, defining, kaminski, lemoine, pradeu, e1009892, 34555119, 8460019, 1371, ppat, 1009892, plos, disparate, concept, bannister, gillespie, eds, wiley, blackwell, 435, 4051, 2665, microbiology, management, emedicine, dushek, merwe, 24636916, 3989030, 153, rebinding, model, feinerman, altan, bonnet, 17825415, 2131735, molimm, 028, mol, quantitative, challenges, alphabeta, belikov, schraven, simeoni, 26471060, 4608155, s12929, 0194, biomedical, graham, nasaspaceflight, com, ready, dragon, launch, milestones, milstein, hagin, lask, reich, zeliger, shezen, ophir, eidelstein, afik, antebi, dustin, reisner, january, 21045195, 3035066, 1182, 283770, 1042, granule, secretion, serving, arron, spanning, osteoimmunology, 28521713, 14579250, 1002, bies, 10352, 1096, bioessays, tatham, gomperts, kramer, amsterdam, elsevier, academic, press, 289632, transduction, gershwin, wilken, raychaudhuri, ruhaak, lebrilla, 25578468, 4340844, autoimmun, glycans, altered, glycan, jennifer, rolland, robyn, hehir, turning, off, today, life, publishing, sun, 2004, 15300249, 2776074, ni1105, 927, programming, shedlock, shen, requirement, 5617, 38040377, 12690201, 1082305, 2003sci, 337s, 337, janssen, lemmens, wolfe, christen, von, herrath, schoenberger, secondary, 6925, 574770, 12594515, nature01441, 2003natur, 852j, 852, ctl, 17129182, 022106, 141548, 171, resource, booklet, niaid, kjer, nielsen, nours, meehan, bhati, kostenko, reantragoon, williamson, purcell, dudek, mcconville, khairallah, 7426, 4419703, 23051753, nature11605, 2012natur, 717k, 717, presents, chua, 27717815, 20733595, icb, 104, 767, martin, soudais, fremont, 19416870, 2688861, 0903196106, 2009pnas, 8290h, 8290, highly, conserved, evolution, serriari, eoche, lamotte, lion, fumery, marcelo, chatelain, barre, nguyen, khac, dupas, treiner, 24450998, 3992039, cei, 12277, 266, bianchini, biasi, simone, ferraro, sola, cossarizza, pinti, 28119072, 11380, 1133283, imlet, 183, letters, hinks, 26778581, 4819138, imm, 12582, 148, airways, howson, salio, cerundolo, 303, 26136743, 4468870, 00303, ussher, klenerman, willberg, 450, 25339949, 4189401, 00450, players, bacterial, eckle, mak, 26468291, 4683245, 1074, jbc, r115, 685990, 30204, 290, chemistry, byproducts, 21458588, 3130845, micinf, 007, 742, napier, adams, 344, 26217338, 4492155, 00344, antimicrobial, mallevaey, fontaine, breuilh, paget, castro, vendeville, capron, leite, moraes, trottein, faveeuw, 17353286, 1865739, iai, 01178, noninvariant, exert, opposite, schistosomiasis, araújo, gama, souza, barros, ribeiro, alves, xabregas, 33506055, 7808823, translating, antitumor, uldrich, moody, burgeoning, family, 1123, 30992456, 26482978, 3298, 1114, singh, schwartz, sandrock, bellemore, nikoopour, 24434314, 3928692, 591, 138, indian, med, res, modulation, abbas, benoist, bluestone, campbell, ghosh, hori, jiang, kuchroo, mathis, roncarolo, sakaguchi, shevach, ziegler, 11294516, 23507634, 2554, 307, nat, recommendations, simplify, nomenclature, marusina, ono, merleev, ogawa, olney, luxardi, miyamura, yilma, villalobos, bergstrom, kronenberg, soulika, adamopoulos, 27894837, 6066671, 001, inexperienced, compartments, implications, lee, 21288770, 3039080, 004, lineage, shin, iwasaki, 23947354, 3748618, 12087, 165, koch, larbi, derhovanessian, özcelik, naumova, pawelec, 18657274, 2515281, 1742, 4933, ageing, multiparameter, cytometric, analysis, young, old, willinger, hasegawa, mcmichael, callan, 2005, 903, 16412760, 16237082, signatures, akbar, terry, timms, beverley, janossy, 1988, 22340282, 2965180, cd45r, gain, uchl1, primed, sallusto, lenig, förster, lipp, lanzavecchia, potentials, 6754, 712, 4378970, 10537110, 44385, 1999natur, 708s, 708, jia, advances, vol, 841, 230, 25261209, 9486, 1007, 9487, 9_8, 209, saravia, chapman, chi, 643, 30867582, 6804569, s41423, 0220, 634, sung, gilman, sachs, kwak, 32973809, 7461801, 02025, recurrent, losses, gutcher, becher, 17476341, 1857272, jci31720, 1119, clin, invest, polarization, haynes, markert, sempowski, hale, 2000, reconstitution, aging, 560, 10837068, annu, rev, 297, pekalski, garcía, ferreira, rainbow, smyth, mashar, brady, savinykh, dopico, mahmood, duley, stevens, walker, cutler, waldron, lynch, dunger, shannon, lowe, coles, wallace, todd, wicker, e93739, 28814669, 5621870, 93739, neonatal, adult, cr1, cr2, hinterberger, aichinger, prazeres, costa, voehringer, hoffmann, klein, 519, 33154019, 20431619, 1874, 512, autonomous
Text of the page (random words):
nt events random article about wikipedia contact us contribute help learn to edit community portal recent changes upload file special pages search search appearance donate create account log in personal tools donate create account log in contents move to sidebar hide top 1 development toggle development subsection 1 1 origin early development and migration to the thymus 1 2 tcr development 1 2 1 tcr β chain selection 1 2 2 positive selection 1 2 3 negative selection 1 2 4 tcr development summary 1 3 thymic output 2 types of t cell toggle types of t cell subsection 2 1 conventional adaptive t cells 2 1 1 helper cd4 t cells 2 1 2 cytotoxic cd8 t cells 2 1 3 memory t cells 2 1 4 regulatory cd4 t cells 2 2 innate like t cells 2 2 1 natural killer t cell 2 2 2 mucosal associated invariant t cells 2 2 3 gamma delta t cells 3 activation toggle activation subsection 3 1 antigen discrimination 4 clinical significance toggle clinical significance subsection 4 1 deficiency 4 2 cancer 4 3 exhaustion 4 3 1 during chronic infection and sepsis 4 3 2 during transplantation 4 3 3 during cancer 5 see also 6 references 7 further reading toggle the table of contents t cell 63 languages العربية مصرى azərbaycanca български বাংলা bosanski català کوردی čeština dansk deutsch ދިވެހިބަސް ελληνικά esperanto español eesti euskara فارسی suomi føroyskt français gaeilge galego עברית हिन्दी hrvatski magyar հայերեն bahasa indonesia italiano 日本語 ქართული қазақша 한국어 kurdî latina lietuvių македонски മലയാളം bahasa melayu nederlands norsk bokmål occitan ਪੰਜਾਬੀ polski português română русский srpskohrvatski српскохрватски සිංහල simple english slovenčina slovenščina shqip српски srpski svenska தமிழ் ไทย türkçe українська اردو tiếng việt 中文 edit links article talk english read edit view history tools tools move to sidebar hide actions read edit view history general what links here related changes upload file permanent link page information cite this page get shortened url print export download as pdf printable version in other projects wikimedia commons wikiversity wikidata item appearance move to sidebar hide from wikipedia the free encyclopedia white blood cells of the immune system t cell 3d render of a standard t cell with an annotated microvillus scanning electron micrograph of a red blood cell left a platelet center and a t lymphocyte right colorized details system immune system identifiers latin lymphocytus t mesh d013601 th h2 00 04 1 02007 fma 62870 anatomical terms of microanatomy edit on wikidata t cells also known as t lymphocytes are an important part of the immune system and play a central role in the adaptive immune response t cells can be distinguished from other lymphocytes by the presence of a t cell receptor tcr on their cell surface t cells are born from hematopoietic stem cells 1 found in the bone marrow developing t cells then migrate to the thymus gland to develop or mature t cells derive their name from the thymus 2 3 after migration to the thymus getting stimulated by thymosin the precursor cells mature into several distinct types of t cells t cell differentiation also continues after they have left the thymus groups of specific differentiated t cell subtypes have a variety of important functions in controlling and shaping the immune response one of these functions is immune mediated cell death and it is carried out by two major subtypes cd8 killer cytotoxic effector tumor antigen specific t cells and cd4 helper t cells each respectively named for the presence of proteins cd8 or cd4 on the cell surface cd8 t cells also known as killer t cells are cytotoxic referring to their ability to directly kill virus infected cells and cancer cells cd8 t cells are also able to use small signalling proteins known as cytokines to recruit other types of cells when mounting an immune response on the other hand cd4 t cells function as helper cells unlike cd8 killer t cells the cd4 helper t t h cells function by further activating memory b cells and cytotoxic t cells which leads to a larger immune response the specific adaptive immune response regulated by the t h cell depends on its subtype i e t helper1 t helper2 t helper17 and regulatory t cell 4 which is distinguished by the types of cytokines they secrete 2 regulatory t cells are yet another distinct population of t cells that provide the critical mechanism of tolerance whereby immune cells are able to distinguish invading cells from self this prevents immune cells from inappropriately reacting against one s own cells known as an autoimmune response for this reason these regulatory t cells have also been called suppressor t cells these same regulatory t cells can also be co opted by cancer cells to prevent the recognition of and an immune response against tumor cells citation needed development edit origin early development and migration to the thymus edit all t cells originate from c kit sca1 haematopoietic stem cells hsc that reside in the bone marrow in some cases the origin might be the foetal 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 5 these clp cells then migrate via the blood to the thymus where they engraft henceforth they are known as thymocytes the immature stage of a t cell the earliest cells which arrived in the thymus are commonly 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 progenitor etp cells 6 these cells will then undergo a round of division and downregulate c kit and are termed double negative one dn1 cells to become t cells the thymocytes must undergo multiple dn stages as well as positive selection and negative selection double negative thymocytes can be identified by the surface expression of cd2 cd5 and cd7 still during the double negative stages cd34 expression stops and cd1 is expressed expression of both cd4 and cd8 makes them double positive and matures into either cd4 or cd8 cells tcr development edit main article t cell receptor a critical step in t cell maturation is making a functional t cell receptor tcr each mature t cell will ultimately contain a unique tcr that reacts to a random pattern allowing the immune system to recognize many different types of pathogens this process is essential in developing immunity to threats that the immune system has not encountered before since due to random variation there will always be at least one tcr to match any new pathogen a thymocyte can only become an active t cell when it survives the process of developing a functional tcr the tcr consists of two major components the alpha and beta chains these both contain random elements designed to produce a wide variety of different tcrs but due to this huge variety they must be tested to make sure they work at all first the thymocytes attempt to create a functional beta chain testing it against a mock alpha chain then they attempt to create a functional alpha chain once a working tcr has been produced the cells then must test if their tcr will identify threats correctly and to do this it is required to recognize the body s major histocompatibility complex mhc in a process known as positive selection the thymocyte must also ensure that it does not react adversely to self antigens called negative selection if both positive and negative selection are successful the tcr becomes fully operational and the thymocyte becomes a t cell tcr β chain selection edit at the dn2 stage cd44 cd25 cells upregulate the recombination genes rag1 and rag2 and re arrange the tcrβ locus combining v d j recombination 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 the thymocyte 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 silence the alternate allele 7 although these signals require the pre tcr at the cell surface they are independent of ligand binding to the pre tcr if the chains successfully pair a pre tcr forms and 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 the tcrα locus during the double positive stage positive selection edit the process of positive selection takes 3 to 4 days and occurs in the thymic cortex 8 double positive thymocytes cd4 cd8 migrate 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 which reside on the surface of cortical epithelial cells only thymocytes that interact well with mhc i or mhc ii will receive a vital survival signal while those that cannot interact strongly enough will receive no signal and die from neglect this process ensures that the surviving thymocytes will have an mhc affinity that means they will exhibit stronger binding affinity for specific mhc alleles in that organism 9 the vast majority of developing thymocytes will not pass positive selection and die during this process 10 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 helper cells whereas thymocytes that interact well with mhc class i molecules mature into cd8 killer cells a thymocyte 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 both cd8 and cd4 cells are now single positive cells 11 this process does not filter for thymocytes that may cause autoimmunity the potentially autoimmune cells are removed by the following process of negative selection which occurs in the thymic medulla negative selection edit negative selection removes thymocytes that are capable of strongly binding with self mhc molecules 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 12 mtecs must be autoimmune regulator positive aire to properly express tissue specific antigens on their mhc class i peptides some mtecs are phagocytosed by thymic dendritic cells this makes them aire antigen presenting cells apcs allowing for presentation of self antigens on mhc class ii molecules positively selected cd4 cells must interact with these 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 t reg cells the remaining cells exit the thymus as mature naive t cells also known as recent thymic emigrants 13 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 tcr development summary edit β selection is the first checkpoint where thymocytes that are able to form a functional pre tcr with an invariant alpha chain and a functional beta chain are allowed to continue development in the thymus next positive selection checks that thymocytes have successfully rearranged their tcrα locus and are capable of recognizing mhc molecules with appropriate affinity negative selection in the medulla then eliminates thymocytes that bind too strongly to self antigens expressed on mhc molecules these selection processes allow for tolerance of self by the immune system typical naive t cells that leave the thymus via the corticomedullary junction are self restricted self tolerant and single positive citation needed thymic output edit about 98 of thymocytes die during the development processes in the thymus by failing either positive selection or negative selection whereas the other 2 survive and leave the thymus to become mature immunocompetent t cells 14 the thymus contributes fewer cells as a person ages as the thymus shrinks by about 3 15 a year throughout middle age a corresponding fall in the thymic production of naive t cells occurs leaving peripheral t cell expansion and regeneration to play a greater role in protecting older people types of t cell edit t cells are grouped into a series of subsets based on their function cd4 and cd8 t cells are selected in the thymus but undergo further differentiation in the periphery to specialized cells which have different functions t cell subsets were initially defined by function but also have associated gene or protein expression patterns conventional adaptive t cells edit helper cd4 t cells edit main article t helper cell depiction of the various key subsets of cd4 positive t cells with corresponding associated cytokines and transcription factors t helper cells t h cells assist other lymphocytes including the maturation of b cells into plasma cells and memory b cells and activation of cytotoxic t cells and macrophages these cells are also known as cd4 t cells as they express the cd4 glycoprotein on their surfaces helper t cells become activated when they are presented with peptide antigens by mhc class ii molecules which are expressed on the surface of antigen presenting cells apcs once activated they divide rapidly and secrete cytokines 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 16 cd4 helper t cell subsets cell type cytokines produced key transcription factor role in immune defense related diseases th1 ifnγ il 2 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 th9 17 18 il 9 irf4 pu 1 defense against helminths parasitic worms and cell dependent allergic inflammation multiple sclerosis tfh il 21 il 4 bcl 6 help b cells produce antibodies asthma and other allergic diseases th22 19 18 il 22 ahr pathogenesis of allergic airway diseases and predominantly anti inflammatory crohn s disease rheumatoid arthritis tumors cytotoxic cd8 t cells edit main article cytotoxic t cell superresolution image of a group of cytotoxic t cells surrounding a cancer cell cytotoxic t ce...
|
