nach oben

Seminars in Immunopathology

Erschienen in:

01.12.2008 | Review

Molecular mechanisms that control mouse and human TCR-αβ and TCR-γδ T cell development

verfasst von: Tom Taghon, Ellen V. Rothenberg

Erschienen in: Seminars in Immunopathology | Ausgabe 4/2008

Einloggen, um Zugang zu erhalten

Abstract

Following specification of hematopoietic precursor cells into the T cell lineage, several developmental options remain available to the immature thymocytes. The paradigm is that the outcome of the T cell receptor rearrangements and the corresponding T cell receptor signaling events will be predominant to determine the first of these choices: the αβ versus γδ T cell pathways. Here, we review the thymus-derived environmental signals, the transcriptional mediators, and other molecular mechanisms that are also involved in this decision in both the mouse and human. We discuss the differences in cellular events between the αβ and γδ developmental pathways and try to correlate these with a corresponding complexity of the molecular mechanisms that support them.

Allman D, Sambandam A, Kim S et al (2003) Thymopoiesis independent of common lymphoid progenitors. Nat Immunol 4:168–174 doi:10.1038/ni878 PubMed

Porritt HE, Rumfelt LL, Tabrizifard S et al (2004) Heterogeneity among DN1 prothymocytes reveals multiple progenitors with different capacities to generate T cell and non-T cell lineages. Immunity 20:735–745 doi:10.1016/j.immuni.2004.05.004 PubMed

Bell JJ, Bhandoola A (2008) The earliest thymic progenitors for T cells possess myeloid lineage potential. Nature 452:764–767 doi:10.1038/nature06840 PubMed

Wada H, Masuda K, Satoh R et al (2008) Adult T-cell progenitors retain myeloid potential. Nature 452:768–772 doi:10.1038/nature06839 PubMed

Rothenberg EV, Taghon T (2005) Molecular genetics of T cell development. Annu Rev Immunol 23:601–649 doi:10.1146/annurev.immunol.23.021704.115737 PubMed

Maillard I, Fang T, Pear WS (2005) Regulation of lymphoid development, differentiation, and function by the Notch pathway. Annu Rev Immunol 23:945–974 doi:10.1146/annurev.immunol.23.021704.115747 PubMed

Radtke F, Wilson A, Mancini SJ et al (2004) Notch regulation of lymphocyte development and function. Nat Immunol 5:247–253 doi:10.1038/ni1045 PubMed

Radtke F, Wilson A, Stark G et al (1999) Deficient T cell fate specification in mice with an induced inactivation of Notch1. Immunity 10:547–558 doi:10.1016/S1074-7613(00)80054-0 PubMed

Wilson A, MacDonald HR, Radtke F (2001) Notch 1-deficient common lymphoid precursors adopt a B cell fate in the thymus. J Exp Med 194:1003–1012 doi:10.1084/jem.194.7.1003 PubMed

10.

Sambandam A, Maillard I, Zediak VP et al (2005) Notch signaling controls the generation and differentiation of early T lineage progenitors. Nat Immunol 6:663–670 doi:10.1038/ni1216 PubMed

11.

Hozumi K, Negishi N, Suzuki D et al (2004) Delta-like 1 is necessary for the generation of marginal zone B cells but not T cells in vivo. Nat Immunol 5:638–644 doi:10.1038/ni1075 PubMed

12.

Schmitt TM, Zuniga-Pflucker JC (2002) Induction of T cell development from hematopoietic progenitor cells by delta-like-1 in vitro. Immunity 17:749–756 doi:10.1016/S1074-7613(02)00474-0 PubMed

13.

Besseyrias V, Fiorini E, Strobl LJ et al (2007) Hierarchy of Notch–Delta interactions promoting T cell lineage commitment and maturation. J Exp Med 204:331–343 doi:10.1084/jem.20061442 PubMed

14.

Jaleco AC, Neves H, Hooijberg E et al (2001) Differential effects of Notch ligands Delta-1 and Jagged-1 in human lymphoid differentiation. J Exp Med 194:991–1002 doi:10.1084/jem.194.7.991 PubMed

15.

Visan I, Yuan JS, Tan JB et al (2006) Regulation of intrathymic T-cell development by Lunatic Fringe–Notch1 interactions. Immunol Rev 209:76–94 doi:10.1111/j.0105-2896.2006.00360.x PubMed

16.

Schmitt TM, Ciofani M, Petrie HT et al (2004) Maintenance of T cell specification and differentiation requires recurrent notch receptor-ligand interactions. J Exp Med 200:469–479 doi:10.1084/jem.20040394 PubMed

17.

Maeda T, Merghoub T, Hobbs RM et al (2007) Regulation of B versus T lymphoid lineage fate decision by the proto-oncogene LRF. Science 316:860–866 doi:10.1126/science.1140881 PubMed

18.

Taghon TN, David ES, Zuniga-Pflucker JC et al (2005) Delayed, asynchronous, and reversible T-lineage specification induced by Notch/Delta signaling. Genes Dev 19:965–978 doi:10.1101/gad.1298305 PubMed

19.

Franco CB, Scripture-Adams DD, Proekt I et al (2006) Notch/Delta signaling constrains reengineering of pro-T cells by PU.1. Proc Natl Acad Sci USA 103:11993–11998 doi:10.1073/pnas.0601188103 PubMed

20.

Taghon T, Yui MA, Rothenberg EV (2007) Mast cell lineage diversion of T lineage precursors by the essential T cell transcription factor GATA-3. Nat Immunol 8:845–855 doi:10.1038/ni1486 PubMed

21.

Laiosa CV, Stadtfeld M, Xie H et al (2006) Reprogramming of committed T cell progenitors to macrophages and dendritic cells by C/EBP alpha and PU.1 transcription factors. Immunity 25:731–744 doi:10.1016/j.immuni.2006.09.011 PubMed

22.

De Smedt M, Taghon T, Van de Walle I et al (2007) Notch signaling induces cytoplasmic CD3 epsilon expression in human differentiating NK cells. Blood 110:2696–2703 doi:10.1182/blood-2007-03-082206 PubMed

23.

Rothenberg EV, Moore JE, Yui MA (2008) Launching the T-cell-lineage developmental programme. Nat Rev Immunol 8:9–21 doi:10.1038/nri2232 PubMed

24.

Chen CH, Sowder JT, Lahti JM et al (1989) TCR3: a third T-cell receptor in the chicken. Proc Natl Acad Sci U S A 86:2351–2355 doi:10.1073/pnas.86.7.2351 PubMed

25.

Six A, Rast JP, McCormack WT et al (1996) Characterization of avian T-cell receptor gamma genes. Proc Natl Acad Sci U S A 93:15329–15334 doi:10.1073/pnas.93.26.15329 PubMed

26.

Gobel TW, Chen CL, Lahti J et al (1994) Identification of T-cell receptor alpha-chain genes in the chicken. Proc Natl Acad Sci USA 91:1094–1098 doi:10.1073/pnas.91.3.1094 PubMed

27.

Rast JP, Anderson MK, Strong SJ et al (1997) alpha, beta, gamma, and delta T cell antigen receptor genes arose early in vertebrate phylogeny. Immunity 6:1–11 doi:10.1016/S1074-7613(00)80237-X PubMed

28.

Litman GW, Anderson MK, Rast JP (1999) Evolution of antigen binding receptors. Annu Rev Immunol 17:109–147 doi:10.1146/annurev.immunol.17.1.109 PubMed

29.

Anderson MK, Pant R, Miracle AL et al (2004) Evolutionary origins of lymphocytes: ensembles of T cell and B cell transcriptional regulators in a cartilaginous fish. J Immunol 172:5851–5860PubMed

30.

Miracle AL, Anderson MK, Litman RT et al (2001) Complex expression patterns of lymphocyte-specific genes during the development of cartilaginous fish implicate unique lymphoid tissues in generating an immune repertoire. Int Immunol 13:567–580 doi:10.1093/intimm/13.4.567 PubMed

31.

Cunningham CP, Kimpton WG, Fernando A et al (2001) Neonatal thymectomy identifies two major pools of sessile and recirculating peripheral T cells which appear to be under separate homeostatic control. Int Immunol 13:1351–1359 doi:10.1093/intimm/13.11.1351 PubMed

32.

Hein WR, Mackay CR (1991) Prominence of gamma delta T cells in the ruminant immune system. Immunol Today 12:30–34 doi:10.1016/0167-5699(91)90109-7 PubMed

33.

Pollock JM, Welsh MD (2002) The WC1(+) gammadelta T-cell population in cattle: a possible role in resistance to intracellular infection. Vet Immunol Immunopathol 89:105–114 doi:10.1016/S0165-2427(02)00200-3 PubMed

34.

Masuda K, Kakugawa K, Nakayama T et al (2007) T cell lineage determination precedes the initiation of TCR beta gene rearrangement. J Immunol 179:3699–3706PubMed

35.

Wilson A, Held W, MacDonald HR (1994) Two waves of recombinase gene expression in developing thymocytes. J Exp Med 179:1355–1360 doi:10.1084/jem.179.4.1355 PubMed

36.

Ciofani M, Knowles GC, Wiest DL et al (2006) Stage-specific and differential notch dependency at the alphabeta and gammadelta T lineage bifurcation. Immunity 25:105–116 doi:10.1016/j.immuni.2006.05.010 PubMed

37.

Kang J, Volkmann A, Raulet DH (2001) Evidence that gammadelta versus alphabeta T cell fate determination is initiated independently of T cell receptor signaling. J Exp Med 193:689–698 doi:10.1084/jem.193.6.689 PubMed

38.

Prinz I, Sansoni A, Kissenpfennig A et al (2006) Visualization of the earliest steps of gammadelta T cell development in the adult thymus. Nat Immunol 7:995–1003 doi:10.1038/ni1371 PubMed

39.

Bonneville M, Ishida I, Mombaerts P et al (1989) Blockage of alpha beta T-cell development by TCR gamma delta transgenes. Nature 342:931–934 doi:10.1038/342931a0 PubMed

40.

von Boehmer H, Bonneville M, Ishida I et al (1988) Early expression of a T-cell receptor beta-chain transgene suppresses rearrangement of the V gamma 4 gene segment. Proc Natl Acad Sci U S A 85:9729–9732 doi:10.1073/pnas.85.24.9729

41.

Ferrero I, Mancini SJ, Grosjean F et al (2006) TCRgamma silencing during alphabeta T cell development depends upon pre-TCR-induced proliferation. J Immunol 177:6038–6043PubMed

42.

Ishida I, Verbeek S, Bonneville M et al (1990) T-cell receptor gamma delta and gamma transgenic mice suggest a role of a gamma gene silencer in the generation of alpha beta T cells. Proc Natl Acad Sci U S A 87:3067–3071 doi:10.1073/pnas.87.8.3067 PubMed

43.

Chien YH, Iwashima M, Kaplan KB et al (1987) A new T-cell receptor gene located within the alpha locus and expressed early in T-cell differentiation. Nature 327:677–682 doi:10.1038/327677a0 PubMed

44.

Wilson A, MacDonald HR (1998) A limited role for beta-selection during gamma delta T cell development. J Immunol 161:5851–5854PubMed

45.

Aifantis I, Azogui O, Feinberg J et al (1998) On the role of the pre-T cell receptor in alphabeta versus gammadelta T lineage commitment. Immunity 9:649–655 doi:10.1016/S1074-7613(00)80662-7 PubMed

46.

Hao QL, George AA, Zhu J et al (2008) Human intrathymic lineage commitment is marked by differential CD7 expression: identification of CD7neg lympho-myeloid thymic progenitors. Blood 111:1318–1326PubMed

47.

Six EM, Bonhomme D, Monteiro M et al (2007) A human postnatal lymphoid progenitor capable of circulating and seeding the thymus. J Exp Med 204:3085–3093 doi:10.1084/jem.20071003 PubMed

48.

Haddad R, Guimiot F, Six E et al (2006) Dynamics of thymus-colonizing cells during human development. Immunity 24:217–230 doi:10.1016/j.immuni.2006.01.008 PubMed

49.

Dik WA, Pike-Overzet K, Weerkamp F et al (2005) New insights on human T cell development by quantitative T cell receptor gene rearrangement studies and gene expression profiling. J Exp Med 201:1715–1723 doi:10.1084/jem.20042524 PubMed

50.

Carrasco YR, Trigueros C, Ramiro AR et al (1999) Beta-selection is associated with the onset of CD8beta chain expression on CD4(+)CD8alphaalpha(+) pre-T cells during human intrathymic development. Blood 94:3491–3498PubMed

51.

Joachims ML, Chain JL, Hooker SW et al (2006) Human alpha beta and gamma delta thymocyte development: TCR gene rearrangements, intracellular TCR beta expression, and gamma delta developmental potential—differences between men and mice. J Immunol 176:1543–1552PubMed

52.

Offner F, Van Beneden K, Debacker V et al (1997) Phenotypic and functional maturation of TCR gammadelta cells in the human thymus. J Immunol 158:4634–4641PubMed

53.

Saint-Ruf C, Panigada M, Azogui O et al (2000) Different initiation of pre-TCR and gammadeltaTCR signalling. Nature 406:524–527 doi:10.1038/35020093 PubMed

54.

Aifantis I, Borowski C, Gounari F et al (2002) A critical role for the cytoplasmic tail of pTalpha in T lymphocyte development. Nat Immunol 3:483–488PubMed

55.

Hayes SM, Li L, Love PE (2005) TCR signal strength influences alphabeta/gammadelta lineage fate. Immunity 22:583–593 doi:10.1016/j.immuni.2005.03.014 PubMed

56.

Haks MC, Lefebvre JM, Lauritsen JP et al (2005) Attenuation of gammadeltaTCR signaling efficiently diverts thymocytes to the alphabeta lineage. Immunity 22:595–606 doi:10.1016/j.immuni.2005.04.003 PubMed

57.

Kreslavsky T, Garbe AI, Krueger A et al (2008) T cell receptor-instructed {alpha}{beta} versus {gamma}{delta} lineage commitment revealed by single-cell analysis. J Exp Med 205:1173–1186 doi:10.1084/jem.20072425 PubMed

58.

Lewis JM, Girardi M, Roberts SJ et al (2006) Selection of the cutaneous intraepithelial gammadelta+ T cell repertoire by a thymic stromal determinant. Nat Immunol 7:843–850 doi:10.1038/ni1363 PubMed

59.

Terrence K, Pavlovich CP, Matechak EO et al (2000) Premature expression of T cell receptor (TCR)alphabeta suppresses TCRgammadelta gene rearrangement but permits development of gammadelta lineage T cells. J Exp Med 192:537–548 doi:10.1084/jem.192.4.537 PubMed

60.

Taghon T, Yui MA, Pant R et al (2006) Developmental and molecular characterization of emerging beta- and gammadelta-selected pre-T cells in the adult mouse thymus. Immunity 24:53–64 doi:10.1016/j.immuni.2005.11.012 PubMed

61.

Carleton M, Haks MC, Smeele SA et al (2002) Early growth response transcription factors are required for development of CD4(-)CD8(-) thymocytes to the CD4(+)CD8(+) stage. J Immunol 168:1649–1658PubMed

62.

Shao H, Kono DH, Chen LY et al (1997) Induction of the early growth response (Egr) family of transcription factors during thymic selection. J Exp Med 185:731–744 doi:10.1084/jem.185.4.731 PubMed

63.

Xi H, Kersh GJ (2004) Early growth response gene 3 regulates thymocyte proliferation during the transition from CD4−CD8− to CD4+CD8+. J Immunol 172:964–971PubMed

64.

Xi H, Schwartz R, Engel I et al (2006) Interplay between RORgammat, Egr3, and E proteins controls proliferation in response to pre-TCR signals. Immunity 24:813–826 doi:10.1016/j.immuni.2006.03.023 PubMed

65.

Plum J, De Smedt M, Leclercq G et al (1996) Interleukin-7 is a critical growth factor in early human T-cell development. Blood 88:4239–4245PubMed

66.

Moore TA, von Freeden-Jeffry U, Murray R et al (1996) Inhibition of gamma delta T cell development and early thymocyte maturation in IL-7 −/− mice. J Immunol 157:2366–2373PubMed

67.

Ye SK, Agata Y, Lee HC et al (2001) The IL-7 receptor controls the accessibility of the TCRgamma locus by Stat5 and histone acetylation. Immunity 15:813–823 doi:10.1016/S1074-7613(01)00230-8 PubMed

68.

Kang J, DiBenedetto B, Narayan K et al (2004) STAT5 is required for thymopoiesis in a development stage-specific manner. J Immunol 173:2307–2314PubMed

69.

Kang J, Coles M, Raulet DH (1999) Defective development of gamma/delta T cells in interleukin 7 receptor-deficient mice is due to impaired expression of T cell receptor gamma genes. J Exp Med 190:973–982 doi:10.1084/jem.190.7.973 PubMed

70.

Yui MA, Rothenberg EV (2004) Deranged early T cell development in immunodeficient strains of nonobese diabetic mice. J Immunol 173:5381–5391PubMed

71.

Huang J, Garrett KP, Pelayo R et al (2005) Propensity of adult lymphoid progenitors to progress to DN2/3 stage thymocytes with Notch receptor ligation. J Immunol 175:4858–4865PubMed

72.

Balciunaite G, Ceredig R, Fehling HJ et al (2005) The role of Notch and IL-7 signaling in early thymocyte proliferation and differentiation. Eur J Immunol 35:1292–1300 doi:10.1002/eji.200425822 PubMed

73.

Wang H, Pierce LJ, Spangrude GJ (2006) Distinct roles of IL-7 and stem cell factor in the OP9-DL1 T-cell differentiation culture system. Exp Hematol 34:1730–1740 doi:10.1016/j.exphem.2006.08.001 PubMed

74.

Yu Q, Erman B, Park JH et al (2004) IL-7 receptor signals inhibit expression of transcription factors TCF-1, LEF-1, and RORgammat: impact on thymocyte development. J Exp Med 200:797–803 doi:10.1084/jem.20032183 PubMed

75.

Okamura RM, Sigvardsson M, Galceran J et al (1998) Redundant regulation of T cell differentiation and TCRalpha gene expression by the transcription factors LEF-1 and TCF-1. Immunity 8:11–20 doi:10.1016/S1074-7613(00)80454-9 PubMed

76.

Sun Z, Unutmaz D, Zou YR et al (2000) Requirement for RORgamma in thymocyte survival and lymphoid organ development. Science 288:2369–2373 doi:10.1126/science.288.5475.2369 PubMed

77.

Goux D, Coudert JD, Maurice D et al (2005) Cooperating pre-T-cell receptor and TCF-1-dependent signals ensure thymocyte survival. Blood 106:1726–1733 doi:10.1182/blood-2005-01-0337 PubMed

78.

Riera-Sans L, Behrens A (2007) Regulation of alphabeta/gammadelta T cell development by the activator protein 1 transcription factor c-Jun. J Immunol 178:5690–5700PubMed

79.

Chappaz S, Flueck L, Farr AG et al (2007) Increased TSLP availability restores T- and B-cell compartments in adult IL-7 deficient mice. Blood 110:3862–3870 doi:10.1182/blood-2007-02-074245 PubMed

80.

Leclercq G, Debacker V, De Smedt M et al (1996) Differential effects of interleukin-15 and interleukin-2 on differentiation of bipotential T/natural killer progenitor cells. J Exp Med 184:325–336 doi:10.1084/jem.184.2.325 PubMed

81.

De Creus A, Van Beneden K, Stevenaert F et al (2002) Developmental and functional defects of thymic and epidermal V gamma 3 cells in IL-15-deficient and IFN regulatory factor-1-deficient mice. J Immunol 168:6486–6493PubMed

82.

Zhao H, Nguyen H, Kang J (2005) Interleukin 15 controls the generation of the restricted T cell receptor repertoire of gamma delta intestinal intraepithelial lymphocytes. Nat Immunol 6:1263–1271 doi:10.1038/ni1267 PubMed

83.

Ohteki T, Yoshida H, Matsuyama T et al (1998) The transcription factor interferon regulatory factor 1 (IRF-1) is important during the maturation of natural killer 1.1+ T cell receptor-alpha/beta+(NK1+T) cells, natural killer cells, and intestinal intraepithelial T cells. J Exp Med 187:967–972 doi:10.1084/jem.187.6.967 PubMed

84.

Melichar H, Kang J (2007) Integrated morphogen signal inputs in gammadelta versus alphabeta T-cell differentiation. Immunol Rev 215:32–45 doi:10.1111/j.1600-065X.2006.00469.x PubMed

85.

Washburn T, Schweighoffer E, Gridley T et al (1997) Notch activity influences the alphabeta versus gammadelta T cell lineage decision. Cell 88:833–843 doi:10.1016/S0092-8674(00)81929-7 PubMed

86.

Garbe AI, Krueger A, Gounari F et al (2006) Differential synergy of Notch and T cell receptor signaling determines alphabeta versus gammadelta lineage fate. J Exp Med 203:1579–1590 doi:10.1084/jem.20060474 PubMed

87.

Wolfer A, Wilson A, Nemir M et al (2002) Inactivation of Notch1 impairs VDJbeta rearrangement and allows pre-TCR-independent survival of early alpha beta Lineage Thymocytes. Immunity 16:869–879 doi:10.1016/S1074-7613(02)00330-8 PubMed

88.

Ciofani M, Zuniga-Pflucker JC (2005) Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism. Nat Immunol 6:881–888 doi:10.1038/ni1234 PubMed

89.

Juntilla MM, Wofford JA, Birnbaum MJ et al (2007) Akt1 and Akt2 are required for alphabeta thymocyte survival and differentiation. Proc Natl Acad Sci USA 104:12105–12110 doi:10.1073/pnas.0705285104 PubMed

90.

Xiong N, Raulet DH (2007) Development and selection of gammadelta T cells. Immunol Rev 215:15–31 doi:10.1111/j.1600-065X.2006.00478.x PubMed

91.

Jiang R, Lan Y, Chapman HD et al (1998) Defects in limb, craniofacial, and thymic development in Jagged2 mutant mice. Genes Dev 12:1046–1057 doi:10.1101/gad.12.7.1046 PubMed

92.

De Smedt M, Hoebeke I, Reynvoet K et al (2005) Different thresholds of Notch signaling bias human precursor cells toward B-, NK-, monocytic/dendritic-, or T-cell lineage in thymus microenvironment. Blood 106:3498–3506 doi:10.1182/blood-2005-02-0496 PubMed

93.

De Smedt M, Reynvoet K, Kerre T et al (2002) Active form of Notch imposes T cell fate in human progenitor cells. J Immunol 169:3021–3029PubMed

94.

De Smedt M, Hoebeke I, Plum J (2004) Human bone marrow CD34+ progenitor cells mature to T cells on OP9-DL1 stromal cell line without thymus microenvironment. Blood Cells Mol Dis 33:227–232 doi:10.1016/j.bcmd.2004.08.007 PubMed

95.

La Motte-Mohs RN, Herer E, Zuniga-Pflucker JC (2005) Induction of T-cell development from human cord blood hematopoietic stem cells by Delta-like 1 in vitro. Blood 105:1431–1439 doi:10.1182/blood-2004-04-1293 PubMed

96.

Garcia-Peydro M, de Yebenes V, Toribio ML (2003) Sustained Notch1 signaling instructs the earliest human intrathymic precursors to adopt a gammadelta T-cell fate in fetal thymus organ culture. Blood 102:2444–2451 doi:10.1182/blood-2002-10-3261 PubMed

97.

Pennington DJ, Silva-Santos B, Shires J et al (2003) The inter-relatedness and interdependence of mouse T cell receptor gammadelta+ and alphabeta+ cells. Nat Immunol 4:991–998 doi:10.1038/ni979 PubMed

98.

Silva-Santos B, Pennington DJ, Hayday AC (2005) Lymphotoxin-mediated regulation of gammadelta cell differentiation by alphabeta T cell progenitors. Science 307:925–928 doi:10.1126/science.1103978 PubMed

99.

Ikawa T, Kawamoto H, Goldrath AW et al (2006) E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment. J Exp Med 203:1329–1342 doi:10.1084/jem.20060268 PubMed

100.

Taniuchi I, Osato M, Egawa T et al (2002) Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development. Cell 111:621–633 doi:10.1016/S0092-8674(02)01111-X PubMed

101.

David-Fung ES, Yui MA, Morales M et al (2006) Progression of regulatory gene expression states in fetal and adult pro-T-cell development. Immunol Rev 209:212–236 doi:10.1111/j.0105-2896.2006.00355.x PubMed

102.

Ichikawa M, Asai T, Saito T et al (2004) AML-1 is required for megakaryocytic maturation and lymphocytic differentiation, but not for maintenance of hematopoietic stem cells in adult hematopoiesis. Nat Med 10:299–304 doi:10.1038/nm997 PubMed

103.

Egawa T, Tillman RE, Naoe Y et al (2007) The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells. J Exp Med 204:1945–1957 doi:10.1084/jem.20070133 PubMed

104.

Woolf E, Brenner O, Goldenberg D et al (2007) Runx3 regulates dendritic epidermal T cell development. Dev Biol 303:703–714 doi:10.1016/j.ydbio.2006.12.005 PubMed

105.

Melichar HJ, Narayan K, Der SD et al (2007) Regulation of gammadelta versus alphabeta T lymphocyte differentiation by the transcription factor SOX13. Science 315:230–233 doi:10.1126/science.1135344 PubMed

106.

Tydell CC, David-Fung ES, Moore JE et al (2007) Molecular dissection of prethymic progenitor entry into the T lymphocyte developmental pathway. J Immunol 179:421–438PubMed

107.

Wakabayashi Y, Watanabe H, Inoue J et al (2003) Bcl11b is required for differentiation and survival of alphabeta T lymphocytes. Nat Immunol 4:533–539 doi:10.1038/ni927 PubMed

108.

Inoue J, Kanefuji T, Okazuka K et al (2006) Expression of TCR alpha beta partly rescues developmental arrest and apoptosis of alpha beta T cells in Bcl11b−/− mice. J Immunol 176:5871–5879PubMed

109.

Anderson MK, Hernandez-Hoyos G, Diamond RA et al (1999) Precise developmental regulation of Ets family transcription factors during specification and commitment to the T cell lineage. Development 126:3131–3148PubMed

110.

Eyquem S, Chemin K, Fasseu M et al (2004) The Ets-1 transcription factor is required for complete pre-T cell receptor function and allelic exclusion at the T cell receptor beta locus. Proc Natl Acad Sci U S A 101:15712–15717 doi:10.1073/pnas.0405546101 PubMed

111.

Anderson SJ, Miyake S, Loh DY (1989) Transcription from a murine T-cell receptor V beta promoter depends on a conserved decamer motif similar to the cyclic AMP response element. Mol Cell Biol 9:4835–4845PubMed

112.

Gottschalk LR, Leiden JM (1990) Identification and functional characterization of the human T-cell receptor beta gene transcriptional enhancer: common nuclear proteins interact with the transcriptional regulatory elements of the T-cell receptor alpha and beta genes. Mol Cell Biol 10:5486–5495PubMed

113.

Kienker LJ, Ghosh MR, Tucker PW (1998) Regulatory elements in the promoter of a murine TCRD V gene segment. J Immunol 161:791–804PubMed

114.

Abrahamsen H, Baillie G, Ngai J et al (2004) TCR- and CD28-mediated recruitment of phosphodiesterase 4 to lipid rafts potentiates TCR signaling. J Immunol 173:4847–4858PubMed

115.

Rudolph D, Tafuri A, Gass P et al (1998) Impaired fetal T cell development and perinatal lethality in mice lacking the cAMP response element binding protein. Proc Natl Acad Sci U S A 95:4481–4486 doi:10.1073/pnas.95.8.4481 PubMed

116.

Eberl G, Littman DR (2004) Thymic origin of intestinal alphabeta T cells revealed by fate mapping of RORgammat+ cells. Science 305:248–251 doi:10.1126/science.1096472 PubMed

117.

He YW, Beers C, Deftos ML et al (2000) Down-regulation of the orphan nuclear receptor ROR gamma t is essential for T lymphocyte maturation. J Immunol 164:5668–5674PubMed

118.

Xie H, Sadim MS, Sun Z (2005) RORgammat recruits steroid receptor coactivators to ensure thymocyte survival. J Immunol 175:3800–3809PubMed

119.

Rothenberg EV, Yui MA (2008) Development of T cells (Chapter 12). In: Paul WE (ed) Fundamental immunology. 6th edn. Lippincott, Williams & Wilkins, New York, pp 376–406

120.

Blom B, Heemskerk MH, Verschuren MC et al (1999) Disruption of alpha beta but not of gamma delta T cell development by overexpression of the helix-loop-helix protein Id3 in committed T cell progenitors. EMBO J 18:2793–2802 doi:10.1093/emboj/18.10.2793 PubMed

121.

Heemskerk MH, Blom B, Nolan G et al (1997) Inhibition of T cell and promotion of natural killer cell development by the dominant negative helix loop helix factor Id3. J Exp Med 186:1597–1602 doi:10.1084/jem.186.9.1597 PubMed

122.

Ikawa T, Fujimoto S, Kawamoto H et al (2001) Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2. Proc Natl Acad Sci U S A 98:5164–5169 doi:10.1073/pnas.091537598 PubMed

123.

Agata Y, Tamaki N, Sakamoto S et al (2007) Regulation of T cell receptor beta gene rearrangements and allelic exclusion by the helix-loop-helix protein, E47. Immunity 27:871–884 doi:10.1016/j.immuni.2007.11.015 PubMed

124.

Jones ME, Zhuang Y (2007) Acquisition of a functional T cell receptor during T lymphocyte development is enforced by HEB and E2A transcription factors. Immunity 27:860–870 doi:10.1016/j.immuni.2007.10.014 PubMed

125.

Engel I, Murre C (2004) E2A proteins enforce a proliferation checkpoint in developing thymocytes. EMBO J 23:202–211 doi:10.1038/sj.emboj.7600017 PubMed

126.

Bain G, Engel I, Robanus Maandag EC et al (1997) E2A deficiency leads to abnormalities in alphabeta T-cell development and to rapid development of T-cell lymphomas. Mol Cell Biol 17:4782–4791PubMed

127.

Wojciechowski J, Lai A, Kondo M et al (2007) E2A and HEB are required to block thymocyte proliferation prior to pre-TCR expression. J Immunol 178:5717–5726PubMed

128.

Ghosh JK, Romanow WJ, Murre C (2001) Induction of a diverse T cell receptor gamma/delta repertoire by the helix–loop–helix proteins E2A and HEB in nonlymphoid cells. J Exp Med 193:769–776 doi:10.1084/jem.193.6.769 PubMed

129.

Langerak AW, Wolvers-Tettero IL, van Gastel-Mol EJ et al (2001) Basic helix–loop–helix proteins E2A and HEB induce immature T-cell receptor rearrangements in nonlymphoid cells. Blood 98:2456–2465 doi:10.1182/blood.V98.8.2456 PubMed

130.

Barndt RJ, Dai M, Zhuang Y (2000) Functions of E2A-HEB heterodimers in T-cell development revealed by a dominant negative mutation of HEB. Mol Cell Biol 20:6677–6685 doi:10.1128/MCB.20.18.6677-6685.2000 PubMed

131.

Barndt R, Dai MF, Zhuang Y (1999) A novel role for HEB downstream or parallel to the pre-TCR signaling pathway during alpha beta thymopoiesis. J Immunol 163:3331–3343PubMed

132.

Murre C (2005) Helix–loop–helix proteins and lymphocyte development. Nat Immunol 6:1079–1086 doi:10.1038/ni1260 PubMed

133.

Engel I, Johns C, Bain G et al (2001) Early thymocyte development is regulated by modulation of E2A protein activity. J Exp Med 194:733–745 doi:10.1084/jem.194.6.733 PubMed

134.

Bain G, Romanow WJ, Albers K et al (1999) Positive and negative regulation of V(D)J recombination by the E2A proteins. J Exp Med 189:289–300 doi:10.1084/jem.189.2.289 PubMed

135.

Schilham MW, Wilson A, Moerer P et al (1998) Critical involvement of Tcf-1 in expansion of thymocytes. J Immunol 161:3984–3991PubMed

136.

Verbeek S, Izon D, Hofhuis F et al (1995) An HMG-box-containing T-cell factor required for thymocyte differentiation. Nature 374:70–74 doi:10.1038/374070a0 PubMed

137.

Weerkamp F, Baert MR, Naber BA et al (2006) Wnt signaling in the thymus is regulated by differential expression of intracellular signaling molecules. Proc Natl Acad Sci U S A 103:3322–3326 doi:10.1073/pnas.0511299103 PubMed

138.

Ohteki T, Wilson A, Verbeek S et al (1996) Selectively impaired development of intestinal T cell receptor gamma delta+ cells and liver CD4+NK1+ T cell receptor alpha beta+ cells in T cell factor-1-deficient mice. Eur J Immunol 26:351–355 doi:10.1002/eji.1830260213 PubMed

139.

Jeannet G, Scheller M, Scarpellino L et al (2008) Long-term, multilineage hematopoiesis occurs in the combined absence of beta-catenin and gamma-catenin. Blood 111:142–149 doi:10.1182/blood-2007-07-102558 PubMed

140.

Ioannidis V, Beermann F, Clevers H et al (2001) The beta-catenin–TCF-1 pathway ensures CD4(+)CD8(+) thymocyte survival. Nat Immunol 2:691–697 doi:10.1038/90623 PubMed

141.

Huang J, Durum SK, Muegge K (2001) Cutting edge: histone acetylation and recombination at the TCR gamma locus follows IL-7 induction. J Immunol 167:6073–6077PubMed

142.

Lee PP, Fitzpatrick DR, Beard C et al (2001) A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival. Immunity 15:763–774 doi:10.1016/S1074-7613(01)00227-8 PubMed

143.

Schwartz YB, Kahn TG, Dellino GI et al (2004) Polycomb silencing mechanisms in Drosophila. Cold Spring Harb Symp Quant Biol 69:301–308 doi:10.1101/sqb.2004.69.301 PubMed

144.

Gebuhr TC, Kovalev GI, Bultman S et al (2003) The role of Brg1, a catalytic subunit of mammalian chromatin-remodeling complexes, in T cell development. J Exp Med 198:1937–1949 doi:10.1084/jem.20030714 PubMed

145.

Miyazaki M, Miyazaki K, Itoi M et al (2008) Thymocyte proliferation induced by pre-T cell receptor signaling is maintained through polycomb gene product Bmi-1-mediated Cdkn2a repression. Immunity 28:231–245 doi:10.1016/j.immuni.2007.12.013 PubMed

146.

Lagresle C, Gardie B, Eyquem S et al (2002) Transgenic expression of the p16(INK4a) cyclin-dependent kinase inhibitor leads to enhanced apoptosis and differentiation arrest of CD4−CD8− immature thymocytes. J Immunol 168:2325–2331PubMed

147.

Neilson JR, Zheng GX, Burge CB et al (2007) Dynamic regulation of miRNA expression in ordered stages of cellular development. Genes Dev 21:578–589 doi:10.1101/gad.1522907 PubMed

148.

Cobb BS, Nesterova TB, Thompson E et al (2005) T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer. J Exp Med 201:1367–1373 doi:10.1084/jem.20050572 PubMed

149.

Anderson SJ, Lauritsen JP, Hartman MG et al (2007) Ablation of ribosomal protein L22 selectively impairs alphabeta T cell development by activation of a p53-dependent checkpoint. Immunity 26:759–772 doi:10.1016/j.immuni.2007.04.012 PubMed

150.

Swainson L, Kinet S, Manel N et al (2005) Glucose transporter 1 expression identifies a population of cycling CD4+CD8+ human thymocytes with high CXCR4-induced chemotaxis. Proc Natl Acad Sci U S A 102:12867–12872 doi:10.1073/pnas.0503603102 PubMed

151.

Park JH, Mitnacht R, Torres-Nagel N et al (1993) T cell receptor ligation induces interleukin (IL) 2R beta chain expression in rat CD4,8 double positive thymocytes, initiating an IL-2-dependent differentiation pathway of CD8 alpha+/beta− T cells. J Exp Med 177:541–546 doi:10.1084/jem.177.2.541 PubMed

Titel: Molecular mechanisms that control mouse and human TCR-αβ and TCR-γδ T cell development
verfasst von: Tom Taghon
Ellen V. Rothenberg
Publikationsdatum: 01.12.2008
Verlag: Springer-Verlag
Erschienen in: Seminars in Immunopathology / Ausgabe 4/2008
Print ISSN: 1863-2297
Elektronische ISSN: 1863-2300
DOI: https://doi.org/10.1007/s00281-008-0134-3

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2008

Adoptive precursor cell therapy to enhance immune reconstitution after hematopoietic stem cell transplantation in mouse and man

Strategies for reconstituting and boosting T cell-based immunity following haematopoietic stem cell transplantation: pre-clinical and clinical approaches

Reconstitution of the immune system after hematopoietic stem cell transplantation in humans

Central tolerance: what have we learned from mice?

The immunopathology of thymic GVHD