152:
and apoptotic cells, which occurs physiologically in peripheral tissues. Antigen-loaded iDCs migrate to the lymph nodes, secrete IL-10, TGF-β and present antigen to the naive T cells without costimulation. If the T cell recognizes the antigen, it is turned into the anergic state, depleted or converted to Treg. iDCs are more potent Treg inducers than lymph node resident DCs.
280:
molecules are upregulated by cytokines (signal 3) in the context of acute inflammation. Without pro-inflammatory cytokines, co-stimulatory molecules will not be expressed on the surface of the antigen presenting cell, and so anergy will result if there is an MHC-TCR interaction between the T cell and the APC. TCR stimulation leads to translocation of
245:
Naive cells must enter and exit a quiescent state at the proper timing in their life cycle. If T cells exit a quiescence prematurely there is a lack of tolerance to potential self-reactive cells. T cells rely on negative regulators to keep them in a quiescence state until they are ready for exit, the
204:
on CD8 T cells to restrict self-reactivity. LNSCs can drive the CD4 T cell tolerance by the presentation of the peptide-MHCII complexes, which they acquired from the DCs. On the other hand, LECs can serve as a self-antigen reservoir and can transport self-antigens to DCs to direct self-peptide-MHCII
262:
Ignorance can be seen in situations where there is not a high enough concentration of antigen to trigger activation. The intrinsic mechanism of ignorance is when the affinity of TCR to antigen is too low to elicit T cell activation. There is also an extrinsic mechanism. Antigens, which are present
331:
Immunopriviledged organs evolved mechanisms in which specialized tissue cells and immune cells can mount an appropriate response without disturbing the specialized tissue. Immunopathogenic disturbances are not present in a variety of specialized organs such as; the eyes, reproductive organs and the
151:
to activate naive T cells. However, immature DCs (iDCs) are able to induce both CD4 and CD8 tolerance. The immunogenic potential of iDCs is weak, because of the low expression of costimulatory molecules and a modest level of MHCII. iDCs perform endocytosis and phagocytosis of foreign antigens
279:
Anergy is a state of functional unresponsiveness induced upon self antigen recognition. T-cells can be made non-responsive to antigens presented if the T-cell engages an MHC molecule on an antigen presenting cell (signal 1) without engagement of costimulatory molecules (signal 2). Co-stimulatory
71:
repertoire contains a significant portion of low-avidity self-reactive T cells. These cells can trigger an autoimmune response, and there are several mechanisms of peripheral tolerance to prevent their activation. Antigen-specific mechanisms of peripheral tolerance include persistent of T cell in
292:
into the nucleus is impaired. This disbalance of transcription factors in T cells results in the expression of several genes involved in forming an anergic state. Anergic T cells show long-lasting epigenetic programming that silences effector cytokine production. Anergy is reversible and T
258:
When self-reactive T cells escape thymic deletion they ay enter an ignorant state. Self-reactive T cells can fail to initiate immune response after recognition of self-antigen. These T cells are not classified as dysfunctional members of the immune response, rather they are antigen-inexperienced
110:
of nTregs shows a high affinity for self-peptides, Induced Tregs (iTreg) develop from conventional naive helper T cells after antigen recognition in presence of TGF-β and IL-2. iTregs are enriched in the gut to establish tolerance to commensal microbiota and harmless food antigens. Regardless of
87:
Dependence of a particular antigen on either central or peripheral tolerance is determined by its abundance in the organism. B Cells have a lower probability that they will express cell surface markers to pose the threat of causing an autoimmune attack. Peripheral tolerance of B cells is largely
348:
Split tolerance describes how some antigens can trigger an immune response in one aspect of the immune system and the same antigen could not trigger a response in another set of immune cells. Since many pathways of immunity are interdependent, they do not all need to be tolerized. For example,
241:
activation after tonic signaling, meaning that T cells may be constitutively activated when not in the presence of a ligand. After antigen exposure and costimulation, naive T cells start the process called quiescence exit, which results in proliferation and effector differentiation.
184:) and CD31 surface markers. Among those, only fibroblastic reticular cells and lymphatic endothelial cells (LECs) were shown to play a role in peripheral tolerance. Both of those populations are able to induce CD8 T cell tolerance by the presentation of the endogenous antigens on
111:
their origin, once present Tregs use several different mechanisms to suppress autoimmune reactions. These include depletion of IL-2 from the environment, secretion of anti-inflammatory cytokines IL-10, TGF-β and IL-35 and induction of apoptosis of effector cells.
322:
interaction. Cell death can be mediated by intrinsic of extrinsic methods as mentioned. In most instances there is an up regulation of death markers or the presence of Bcl-2 proteins, which are proteins that are essential in facilitating programmed cell death.
270:
T cells can overcome ignorance through a sufficient signal from signaling molecules (cytokines, infection, inflammatory stimuli, etc.) and induce an autoimmune response. In the inflammatory context, T cells can override ignorance and induce autoimmune disease.
249:
As cells exit a quiescent state they will up regulate enzymes that are responsible for production of essential pathways (nucleic acids, proteins, carbohydrates, etc.). At this stage the T cell will enter the cell cycle and continue to be metabolically active.
66:
Self reactive cells are subject to clonal deletion or clonal diversion. Both processes of peripheral tolerance control the presence and production of self reactive immune cells. Deletion of self-reactive T cells in the thymus is only 60-70% efficient, and
263:
in generally low numbers, can´t stimulate T cells sufficiently. Additionally, there are anatomical barriers that prohibit the activation of these T cells. These specialized mechanisms ensuring ignorance by the immune system have developed in so-called
305:
After T cell response to co-stimulation-deficient antigen, a minor population of T cells develop anergy and a large proportion of T cells are rapidly lost by apoptosis. This cell death can be mediated by intrinsic pro-apoptotic family member
101:
Tregs are the central mediators of immune suppression and they play a key role in maintaining peripheral tolerance. The master regulator of Treg phenotype and function is Foxp3. Natural Tregs (nTregs) are generated in the thymus during the
301:
Before release into the periphery T cells are subjected to thymic deletion if they prove to have the capacity to react with self. Peripheral deletion is the disposal of potential self reactive T cells that escaped thymic deletion.
733:
Malhotra, Deepali; Linehan, Jonathan L; Dileepan, Thamotharampillai; Lee, You Jeong; Purtha, Whitney E; Lu, Jennifer V; Nelson, Ryan W; Fife, Brian T; Orr, Harry T; Anderson, Mark S; Hogquist, Kristin A; Jenkins, Marc K (2016).
168:(IDO) to prevent T cell proliferation. Retinoic acid is secreted to support iTreg differentiation, too. Nonetheless, upon maturation (for example during the infection) DCs largely lose their tolerogenic capabilities.
1142:
Fletcher, Anne L.; Lukacs-Kornek, Veronika; Reynoso, Erika D.; Pinner, Sophie E.; Bellemare-Pelletier, Angelique; Curry, Mark S.; Collier, Ai-Ris; Boyd, Richard L.; Turley, Shannon J. (2010-04-12).
246:
down regulation of negative regulators increases T cell activation. Premature and over activation of T cells can lead to harmful down stream responses and possibly trigger an autoimmune response.
332:
central nervous system. These areas are protected by several mechanisms: Fas-ligand expression binds Fas on lymphocytes inducing apoptosis, anti-inflammatory cytokines (including TGF-beta and
221:, low affinity self-reactive T cells continuously escape to the immune periphery. Therefore, additional mechanisms exist to prevent self-reactive and unrestained T cells responses.
1314:
Dubrot, Juan; Duraes, Fernanda V.; Potin, Lambert; Capotosti, Francesca; Brighouse, Dale; Suter, Tobias; LeibundGut-Landmann, Salomé; Garbi, Natalio; Reith, Walter (2014-06-02).
1199:
Cohen, Jarish N.; Guidi, Cynthia J.; Tewalt, Eric F.; Qiao, Hui; Rouhani, Sherin J.; Ruddell, Alanna; Farr, Andrew G.; Tung, Kenneth S.; Engelhard, Victor H. (2010-04-12).
176:
Aside from dendritic cells, additional cell populations were identified that are able to induce antigen-specific T cell tolerance. These are mainly the members of
84:(DCs) participate in the negative selection of autoreactive T cells in the thymus, but they also mediate peripheral immune tolerance through several mechanisms.
378:
80:. Tregs, which are also generated during thymic T cell development, further suppress the effector functions of conventional lymphocytes in the periphery.
1906:
237:
and they have low metabolic, transcriptional and translational activities, but still retain the capacity to enter the cell cycle. Quiescence can prevent
1372:
314:
determine the eventual fate of the tolerized T cell. There are also extrinsic mechanisms of deletion mediated by the cytotoxic activity of
1811:
259:
naive cells that will remain in circulation. These cells remain the ability to become activated if in the presence of the correct stimuli.
1144:"Lymph node fibroblastic reticular cells directly present peripheral tissue antigen under steady-state and inflammatory conditions"
1899:
1316:"Lymph node stromal cells acquire peptide–MHCII complexes from dendritic cells and induce antigen-specific CD4+ T cell tolerance"
998:"Immunomodulatory Functions of BTLA and HVEM Govern Induction of Extrathymic Regulatory T Cells and Tolerance by Dendritic Cells"
1201:"Lymph node–resident lymphatic endothelial cells mediate peripheral tolerance via Aire-independent direct antigen presentation"
127:
DCs are a major cell population responsible for the initiation of the adaptive immune response. They present short peptides on
633:
Cretney, Erika; Kallies, Axel; Nutt, Stephen L. (2013). "Differentiation and function of Foxp3+ effector regulatory T cells".
136:
736:"Tolerance is established in polyclonal CD4+ T cells by distinct mechanisms, according to self-peptide expression patterns"
1750:
Macián, Fernando; Garcı́a-Cózar, Francisco; Im, Sin-Hyeog; Horton, Heidi F.; Byrne, Michael C.; Rao, Anjana (2002-06-14).
996:
Jones, Andrew; Bourque, Jessica; Kuehm, Lindsey; Opejin, Adeleye; Teague, Ryan M.; Gross, Cindy; Hawiger, Daniel (2016).
132:
1892:
72:
quiescence, ignorance of antigen and direct inactivation of effector T cells by either clonal deletion, conversion to
388:
2238:
1107:
Koning, Jasper J.; Mebius, Reina E. (2012). "Interdependence of stromal and immune cells for lymph node function".
206:
201:
103:
2233:
1812:"Peripheral Deletion of Antigen-Specific T Cells Leads to Long-Term Tolerance Mediated by CD8+ Cytotoxic Cells"
2176:
209:(mLN), LNSCs can induce Tregs directly by secretion of TGF-β or indirectly by imprinting mLN-resident DCs.
840:
Kanamori, Mitsuhiro; Nakatsukasa, Hiroko; Okada, Masahiro; Lu, Qianjin; Yoshimura, Akihiko (2016-11-01).
165:
88:
mediated by B cell dependence on T cell help. However, B cell peripheral tolerance is much less studied.
2062:
841:
289:
1884:
217:
Although the majority of self-reactive T cell clones are deleted in the thymus by the mechanisms of
180:(LNSCs). LNSCs are generally divided into several subpopulations based on the expression of gp38 (
55:. Peripheral tolerance can also serve a purpose in preventing an immune response to harmless food
2242:
2000:
1850:
177:
404:
Soyer, O. U.; Akdis, M.; Ring, J.; Behrendt, H.; Crameri, R.; Lauener, R.; Akdis, C. A. (2013).
2335:
2264:
1982:
1918:
233:, they are in a quiescent state. That means they are in the non-proliferative, G0 stage of the
44:
2211:
2067:
2045:
1603:
965:
948:
2228:
2072:
1996:
1048:
Domogalla, Matthias P.; Rostan, Patricia V.; Raker, Verena K.; Steinbrink, Kerstin (2017).
189:
1604:"Too dangerous to ignore: self-tolerance and the control of ignorant autoreactive T cells"
8:
2340:
2288:
2223:
2206:
2040:
1958:
48:
293:
cells can recover their functional responsiveness in the absence of the antigen.
139:, DCs start the secretion of proinflammatory cytokines, express costimulatory molecules
2108:
1789:
1727:
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1645:
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1462:
1405:
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997:
921:
888:
817:
784:
760:
735:
707:
672:
612:
564:
495:
462:
443:
131:, which are recognized by specific TCR. After encountering an antigen with recognition
52:
1866:
1768:
1751:
2156:
1922:
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1831:
1781:
1773:
1732:
1714:
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218:
73:
32:
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1706:
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1400:
1384:
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1228:
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1116:
1079:
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916:
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747:
702:
684:
642:
616:
596:
540:
490:
474:
417:
319:
264:
28:
1445:
349:
tolerized T cells will not activate auto-reactive B cells. Without this help from
2171:
1560:
1013:
337:
107:
1827:
478:
156:
is a crucial molecule for DCs mediated Treg conversion. Tolerogenic DCs express
2198:
2143:
2084:
2004:
1977:
544:
529:"Rethinking peripheral T cell tolerance: checkpoints across a T cell's journey"
333:
81:
1502:
1276:
904:
2329:
2166:
2055:
1835:
1777:
1718:
1710:
1661:
1627:
1510:
1453:
1396:
1339:
1284:
1224:
1167:
1120:
1075:
1066:
1050:"Tolerance through Education: How Tolerogenic Dendritic Cells Shape Immunity"
974:
912:
865:
857:
808:
698:
689:
646:
552:
486:
431:
350:
77:
1849:
Streilein, J. Wayne; Takeuchi, Masaharu; Taylor, Andrew W. (February 1997).
1315:
842:"Induced Regulatory T Cells: Their Development, Stability, and Applications"
16:
Removal of autoreactive T and B cells outside of the primary lymphoid organs
2133:
2118:
2113:
2050:
1948:
1785:
1736:
1679:
1619:
1588:
1569:
1518:
1471:
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873:
826:
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608:
560:
504:
439:
315:
238:
128:
68:
1874:
947:
Steinman, Ralph M.; Hawiger, Daniel; Nussenzweig, Michel C. (2003-04-01).
1331:
1216:
1159:
587:
Mueller, Daniel L (2010). "Mechanisms maintaining peripheral tolerance".
185:
1851:"Immune privilege, T-cell tolerance, and tissue-restricted autoimmunity"
1810:
Herndon, John M.; Stuart, Patrick M.; Ferguson, Thomas A. (2005-04-01).
119:
mediated costimulation of T cells after TCR antigen recognition.
2256:
2009:
1915:
1388:
234:
164:
to directly induce apoptosis of responding T cells. They also produce
157:
148:
20:
800:
422:
405:
310:. The balance between proapoptotic BIM and the antiapoptotic mediator
212:
2314:
2019:
1914:
1646:"Tolerance and exhaustion: defining mechanisms of T cell dysfunction"
192:, and the production of autoantigens depends on transcription factor
751:
600:
2304:
2089:
2077:
2035:
1989:
1953:
60:
1485:
Chapman, Nicole M.; Boothby, Mark R.; Chi, Hongbo (January 2020).
1141:
2309:
2123:
1972:
1943:
1430:"Strategies to Address Chimeric Antigen Receptor Tonic Signaling"
785:"The role of inhibitory signaling in peripheral B cell tolerance"
307:
56:
2281:
2269:
2014:
1965:
288:
signaling in T cells and translocation of transcription factor
284:
into the nucleus. In the absence of costimulation, there is no
230:
112:
40:
36:
1261:"Lymph node stromal cells: cartographers of the immune system"
1047:
673:"Mechanisms of Tolerance Induction by Dendritic Cells In Vivo"
311:
197:
193:
161:
1752:"Transcriptional Mechanisms Underlying Lymphocyte Tolerance"
1487:"Metabolic coordination of T cell quiescence and activation"
1749:
1644:
Schietinger, Andrea; Greenberg, Philip D. (February 2014).
887:
Dominguez-Villar, Margarita; Hafler, David A. (July 2018).
285:
281:
181:
153:
144:
140:
116:
51:
T and B cells which escaped central tolerance do not cause
1373:"Stem cell quiescence: the challenging path to activation"
1313:
1259:
Krishnamurty, Akshay T.; Turley, Shannon J. (April 2020).
946:
839:
732:
527:
ElTanbouly, Mohamed A.; Noelle, Randolph J. (April 2021).
115:
is a surface molecule present on Tregs which can prevent
1848:
995:
91:
1543:
Marescal, Océane; Cheeseman, Iain M. (November 2020).
886:
403:
1809:
1693:
Kalekar, Lokesh A.; Mueller, Daniel L. (2017-04-01).
1805:
1803:
1643:
1198:
1695:"Relationship between CD4 Tregs and anergy in vivo"
213:
Intrinsic mechanisms of T cell peripheral tolerance
1545:"Cellular Mechanisms and Regulation of Quiescence"
1258:
632:
1800:
1602:Parish, Ian A; Heath, William R (February 2008).
1542:
1484:
670:
406:"Mechanisms of peripheral tolerance to allergens"
35:. It takes place in the immune periphery (after
2327:
526:
1692:
1900:
671:Hasegawa, Hitoshi; Matsumoto, Takuya (2018).
461:Xing, Yan; Hogquist, Kristin A. (June 2012).
1371:Urbán, Noelia; Cheung, Tom H. (2021-02-01).
1106:
460:
1601:
1370:
1907:
1893:
1427:
889:"Regulatory T cells in autoimmune disease"
467:Cold Spring Harbor Perspectives in Biology
463:"T-Cell Tolerance: Central and Peripheral"
326:
1767:
1726:
1669:
1578:
1568:
1461:
1404:
1347:
1232:
1175:
1083:
1065:
1021:
964:
920:
816:
759:
706:
688:
494:
421:
372:
370:
368:
366:
966:10.1146/annurev.immunol.21.120601.141040
188:molecules. LNSCs lack expression of the
1428:Ajina, Adam; Maher, John (2018-09-01).
782:
586:
376:
2328:
1639:
1637:
1538:
1536:
363:
296:
137:pathogen-associated molecular patterns
47:). Its main purpose is to ensure that
1888:
1254:
1252:
1043:
1041:
942:
940:
353:, the B cells will not be activated.
96:
728:
726:
666:
664:
628:
626:
582:
580:
578:
522:
520:
518:
516:
514:
92:Cells mediating peripheral tolerance
1634:
1533:
13:
1249:
1038:
937:
343:
122:
14:
2352:
723:
661:
623:
575:
511:
1320:Journal of Experimental Medicine
1205:Journal of Experimental Medicine
1148:Journal of Experimental Medicine
336:) and blood-tissue-barrier with
205:presentation to CD4 T cells. In
1842:
1743:
1686:
1595:
1478:
1421:
1364:
1307:
1192:
1135:
1100:
989:
880:
833:
377:Janeway, Charles (2001-01-01).
2234:Immunoglobulin class switching
776:
454:
397:
1:
1867:10.1016/S0198-8859(96)00288-1
1769:10.1016/S0092-8674(02)00767-5
1608:Immunology & Cell Biology
1446:10.1158/1535-7163.mct-17-1097
1434:Molecular Cancer Therapeutics
949:"Tolerogenic dendritic cells"
356:
224:
1561:10.1016/j.devcel.2020.09.029
1014:10.1016/j.immuni.2016.10.008
783:Getahun, Andrew (May 2022).
253:
229:When naive T cells exit the
7:
1828:10.4049/jimmunol.174.7.4098
953:Annual Review of Immunology
479:10.1101/cshperspect.a006957
340:between endothelial cells.
166:indoleamine 2,3-dioxygenase
10:
2357:
2063:Polyclonal B cell response
545:10.1038/s41577-020-00454-2
2297:
2255:
2197:
2098:
2028:
1936:
1929:
1816:The Journal of Immunology
1503:10.1038/s41577-019-0203-y
1491:Nature Reviews Immunology
1277:10.1038/s41590-020-0635-3
905:10.1038/s41590-018-0120-4
533:Nature Reviews Immunology
274:
1711:10.4049/jimmunol.1602031
1662:10.1016/j.it.2013.10.001
1121:10.1016/j.it.2011.10.006
1067:10.3389/fimmu.2017.01764
858:10.1016/j.it.2016.08.012
690:10.3389/fimmu.2018.00350
647:10.1016/j.it.2012.11.002
265:immune privileged organs
178:lymph node stromal cells
171:
76:(Tregs) or induction of
27:is the second branch of
1054:Frontiers in Immunology
677:Frontiers in Immunology
327:Immunoprivileged organs
45:primary lymphoid organs
29:immunological tolerance
2177:Tolerance in pregnancy
1919:adaptive immune system
1620:10.1038/sj.icb.7100161
207:mesenteric lymph nodes
2212:Somatic hypermutation
2046:Polyclonal antibodies
2041:Monoclonal antibodies
1699:Journal of Immunology
789:Immunological Reviews
2229:Junctional diversity
1997:Antigen presentation
1650:Trends in Immunology
1332:10.1084/jem.20132000
1217:10.1084/jem.20092465
1160:10.1084/jem.20092642
1109:Trends in Immunology
846:Trends in Immunology
635:Trends in Immunology
190:autoimmune regulator
25:peripheral tolerance
2224:V(D)J recombination
2207:Affinity maturation
1959:Antigenic variation
297:Peripheral deletion
147:and migrate to the
1549:Developmental Cell
1389:10.1242/dev.165084
380:Immunobiology Five
104:negative selection
97:Regulatory T cells
74:regulatory T cells
53:autoimmune disease
2323:
2322:
2251:
2250:
2001:professional APCs
1265:Nature Immunology
893:Nature Immunology
801:10.1111/imr.13070
740:Nature Immunology
589:Nature Immunology
423:10.1111/all.12085
219:central tolerance
33:central tolerance
2348:
2217:Clonal selection
2189:Immune privilege
2184:Immunodeficiency
2139:Cross-reactivity
2129:Hypersensitivity
1934:
1933:
1909:
1902:
1895:
1886:
1885:
1879:
1878:
1855:Human Immunology
1846:
1840:
1839:
1822:(7): 4098–4104.
1807:
1798:
1797:
1771:
1747:
1741:
1740:
1730:
1705:(7): 2527–2533.
1690:
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1683:
1673:
1641:
1632:
1631:
1599:
1593:
1592:
1582:
1572:
1540:
1531:
1530:
1482:
1476:
1475:
1465:
1440:(9): 1795–1815.
1425:
1419:
1418:
1408:
1383:(3): dev165084.
1368:
1362:
1361:
1351:
1326:(6): 1153–1166.
1311:
1305:
1304:
1256:
1247:
1246:
1236:
1196:
1190:
1189:
1179:
1139:
1133:
1132:
1104:
1098:
1097:
1087:
1069:
1045:
1036:
1035:
1025:
1008:(5): 1066–1077.
993:
987:
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2172:Clonal deletion
2100:
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1808:
1801:
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1570:1721.1/138195.2
1541:
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1422:
1369:
1365:
1312:
1308:
1257:
1250:
1197:
1193:
1140:
1136:
1105:
1101:
1046:
1039:
994:
990:
945:
938:
885:
881:
852:(11): 803–811.
838:
834:
781:
777:
752:10.1038/ni.3327
731:
724:
669:
662:
631:
624:
601:10.1038/ni.1817
585:
576:
525:
512:
459:
455:
402:
398:
391:
383:. Garland Pub.
375:
364:
359:
346:
344:Split tolerance
338:tight junctions
329:
318:/FasL or TRAIL/
299:
277:
256:
227:
215:
196:. LECs express
174:
125:
123:Tolerogenic DCs
99:
94:
82:Dendritic cells
17:
12:
11:
5:
2354:
2344:
2343:
2338:
2321:
2320:
2318:
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2312:
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2203:
2201:
2199:Immunogenetics
2195:
2194:
2192:
2191:
2186:
2181:
2180:
2179:
2174:
2169:
2164:
2159:
2147:
2146:
2144:Co-stimulation
2141:
2136:
2131:
2126:
2121:
2116:
2111:
2104:
2102:
2096:
2095:
2093:
2092:
2087:
2085:Immune complex
2081:
2080:
2075:
2070:
2065:
2060:
2059:
2058:
2053:
2048:
2043:
2032:
2030:
2026:
2025:
2023:
2022:
2017:
2012:
2007:
2005:Dendritic cell
1993:
1992:
1987:
1986:
1985:
1983:Conformational
1980:
1969:
1968:
1963:
1962:
1961:
1956:
1951:
1940:
1938:
1931:
1927:
1926:
1912:
1911:
1904:
1897:
1889:
1881:
1880:
1861:(2): 138–143.
1841:
1799:
1762:(6): 719–731.
1742:
1685:
1633:
1614:(2): 146–152.
1594:
1555:(3): 259–271.
1532:
1477:
1420:
1363:
1306:
1271:(4): 369–380.
1248:
1211:(4): 681–688.
1191:
1154:(4): 689–697.
1134:
1115:(6): 264–270.
1099:
1037:
988:
959:(1): 685–711.
936:
899:(7): 665–673.
879:
832:
775:
746:(2): 187–195.
722:
660:
622:
574:
539:(4): 257–267.
510:
473:(6): a006957.
453:
416:(2): 161–170.
396:
389:
361:
360:
358:
355:
345:
342:
334:interleukin 10
328:
325:
298:
295:
276:
273:
255:
252:
226:
223:
214:
211:
173:
170:
124:
121:
98:
95:
93:
90:
15:
9:
6:
4:
3:
2:
2353:
2342:
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2337:
2336:Immune system
2334:
2333:
2331:
2316:
2313:
2311:
2308:
2306:
2303:
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2300:
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2240:
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2227:
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2222:
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2210:
2209:
2208:
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2204:
2202:
2200:
2196:
2190:
2187:
2185:
2182:
2178:
2175:
2173:
2170:
2168:
2167:Clonal anergy
2165:
2163:
2160:
2158:
2155:
2154:
2153:
2149:
2148:
2145:
2142:
2140:
2137:
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2110:
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2103:
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2088:
2086:
2083:
2082:
2079:
2076:
2074:
2071:
2069:
2066:
2064:
2061:
2057:
2056:Microantibody
2054:
2052:
2049:
2047:
2044:
2042:
2039:
2038:
2037:
2034:
2033:
2031:
2027:
2021:
2018:
2016:
2013:
2011:
2008:
2006:
2002:
1998:
1995:
1994:
1991:
1988:
1984:
1981:
1979:
1976:
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1971:
1970:
1967:
1964:
1960:
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1955:
1952:
1950:
1947:
1946:
1945:
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1941:
1939:
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1932:
1928:
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1920:
1917:
1910:
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1007:
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984:
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962:
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954:
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943:
941:
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902:
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836:
828:
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771:
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390:9780815336426
386:
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294:
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272:
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118:
114:
109:
105:
89:
85:
83:
79:
75:
70:
64:
62:
58:
54:
50:
49:self-reactive
46:
42:
38:
34:
30:
26:
22:
2161:
2134:Inflammation
2119:Alloimmunity
2114:Autoimmunity
2099:Immunity vs.
2051:Autoantibody
1949:Superantigen
1858:
1854:
1844:
1819:
1815:
1759:
1755:
1745:
1702:
1698:
1688:
1656:(2): 51–60.
1653:
1649:
1611:
1607:
1597:
1552:
1548:
1497:(1): 55–70.
1494:
1490:
1480:
1437:
1433:
1423:
1380:
1376:
1366:
1323:
1319:
1309:
1268:
1264:
1208:
1204:
1194:
1151:
1147:
1137:
1112:
1108:
1102:
1057:
1053:
1005:
1001:
991:
956:
952:
896:
892:
882:
849:
845:
835:
795:(1): 27–42.
792:
788:
778:
743:
739:
680:
676:
641:(2): 74–80.
638:
634:
595:(1): 21–27.
592:
588:
536:
532:
470:
466:
456:
413:
409:
399:
379:
347:
330:
304:
300:
278:
269:
261:
257:
248:
244:
239:naive T cell
228:
216:
175:
126:
100:
86:
69:naive T cell
65:
43:egress from
24:
18:
2257:Lymphocytes
1916:Lymphocytic
1377:Development
351:CD4 T cells
149:lymph nodes
2341:Immunology
2330:Categories
2298:Substances
2162:Peripheral
2150:Inaction:
2029:Antibodies
2010:Macrophage
1923:complement
357:References
235:cell cycle
225:Quiescence
200:to engage
21:immunology
2315:Cytolysin
2305:Cytokines
2152:Tolerance
2101:tolerance
2020:Immunogen
1836:0022-1767
1778:0092-8674
1719:0022-1767
1628:0818-9641
1527:199542651
1511:1474-1741
1454:1535-7163
1397:0950-1991
1340:0022-1007
1301:214618784
1285:1529-2916
1225:0022-1007
1168:0022-1007
1076:1664-3224
975:0732-0582
913:1529-2916
866:1471-4906
809:0105-2896
699:1664-3224
569:224808870
553:1474-1741
487:1943-0264
432:1398-9995
254:Ignorance
61:allergens
2265:Cellular
2109:Immunity
2107:Action:
2090:Paratope
2078:Idiotype
2068:Allotype
2036:Antibody
1990:Mimotope
1954:Allergen
1937:Antigens
1930:Lymphoid
1794:15599878
1786:12086671
1737:28320913
1680:24210163
1589:33171109
1519:31406325
1472:30181329
1415:33558315
1358:24842370
1293:32205888
1243:20308365
1186:20308362
1129:22153930
1094:29375543
1060:: 1764.
1032:27793593
1002:Immunity
983:12615891
931:29925983
874:27623114
827:35128676
770:26726812
717:29535726
655:23219401
609:20016506
561:33077935
505:22661634
448:24008758
440:23253293
57:antigens
31:, after
2310:Opsonin
2289:NK cell
2277:Humoral
2157:Central
2124:Allergy
2073:Isotype
1973:Epitope
1944:Antigen
1875:9077562
1728:5363282
1671:3946600
1580:7665062
1463:6130819
1406:7888710
1349:4042642
1234:2856027
1177:2856033
1085:5770648
1023:5112132
922:7882196
818:8986582
761:4718891
708:5834484
683:: 350.
617:9612138
496:3367546
410:Allergy
41:B cells
2282:B cell
2270:T cell
2015:B cell
1978:Linear
1966:Hapten
1873:
1834:
1792:
1784:
1776:
1735:
1725:
1717:
1678:
1668:
1626:
1587:
1577:
1525:
1517:
1509:
1470:
1460:
1452:
1413:
1403:
1395:
1356:
1346:
1338:
1299:
1291:
1283:
1241:
1231:
1223:
1184:
1174:
1166:
1127:
1092:
1082:
1074:
1030:
1020:
981:
973:
929:
919:
911:
872:
864:
825:
815:
807:
768:
758:
715:
705:
697:
653:
615:
607:
567:
559:
551:
503:
493:
485:
446:
438:
430:
387:
320:TRAILR
275:Anergy
231:thymus
133:danger
113:CTLA-4
78:anergy
1790:S2CID
1523:S2CID
1297:S2CID
613:S2CID
565:S2CID
444:S2CID
312:BCL-2
198:PD-L1
194:Deaf1
172:LNSCs
162:TRAIL
129:MHCII
1921:and
1871:PMID
1832:ISSN
1782:PMID
1774:ISSN
1756:Cell
1733:PMID
1715:ISSN
1676:PMID
1624:ISSN
1585:PMID
1515:PMID
1507:ISSN
1468:PMID
1450:ISSN
1411:PMID
1393:ISSN
1354:PMID
1336:ISSN
1289:PMID
1281:ISSN
1239:PMID
1221:ISSN
1182:PMID
1164:ISSN
1125:PMID
1090:PMID
1072:ISSN
1028:PMID
979:PMID
971:ISSN
927:PMID
909:ISSN
870:PMID
862:ISSN
823:PMID
805:ISSN
766:PMID
713:PMID
695:ISSN
651:PMID
605:PMID
557:PMID
549:ISSN
501:PMID
483:ISSN
436:PMID
428:ISSN
385:ISBN
290:AP-1
286:MAPK
282:NFAT
202:PD-1
186:MHCI
182:PDPN
160:and
158:FasL
154:BTLA
145:CD86
143:and
141:CD80
117:CD28
59:and
39:and
2243:HLA
2239:MHC
1863:doi
1824:doi
1820:174
1764:doi
1760:109
1723:PMC
1707:doi
1703:198
1666:PMC
1658:doi
1616:doi
1575:PMC
1565:hdl
1557:doi
1499:doi
1458:PMC
1442:doi
1401:PMC
1385:doi
1381:148
1344:PMC
1328:doi
1324:211
1273:doi
1229:PMC
1213:doi
1209:207
1172:PMC
1156:doi
1152:207
1117:doi
1080:PMC
1062:doi
1018:PMC
1010:doi
961:doi
917:PMC
901:doi
854:doi
813:PMC
797:doi
793:307
756:PMC
748:doi
703:PMC
685:doi
643:doi
597:doi
541:doi
491:PMC
475:doi
418:doi
316:Fas
308:BIM
135:or
108:TCR
19:In
2332::
2003::
1869:.
1859:52
1857:.
1853:.
1830:.
1818:.
1814:.
1802:^
1788:.
1780:.
1772:.
1758:.
1754:.
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1721:.
1713:.
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1610:.
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1287:.
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1237:.
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1070:.
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1040:^
1026:.
1016:.
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1000:.
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37:T
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