CD4 Helper and CD8 Cytotoxic T Cell Differentiation

Literature Cited

1. Boehm T, Bleul CC. 1.  2006. Thymus-homing precursors and the thymic microenvironment. Trends Immunol 27477–84 [Google Scholar]
2. Zhang SL, Bhandoola A. 2.  2014. Trafficking to the thymus. Curr. Top. Microbiol. Immunol. 37387–111 [Google Scholar]
3. Liu C, Saito F, Liu Z, Lei Y, Uehara S. 3.  et al. 2006. Coordination between CCR7- and CCR9-mediated chemokine signals in prevascular fetal thymus colonization. Blood 1082531–39 [Google Scholar]
4. Yui MA, Rothenberg EV. 4.  2014. Developmental gene networks: a triathlon on the course to T cell identity. Nat. Rev. Immunol. 14529–45 [Google Scholar]
5. Ellmeier W, Sawada S, Littman DR. 5.  1999. The regulation of CD4 and CD8 coreceptor gene expression during T cell development. Annu. Rev. Immunol. 17523–54 [Google Scholar]
6. Li L, Leid M, Rothenberg EV. 6.  2010. An early T cell lineage commitment checkpoint dependent on the transcription factor Bcl11b. . Science 32989–93 [Google Scholar]
7. Ikawa T, Hirose S, Masuda K, Kakugawa K, Satoh R. 7.  et al. 2010. An essential developmental checkpoint for production of the T cell lineage. Science 32993–96 [Google Scholar]
8. Li P, Burke S, Wang J, Chen X, Ortiz M. 8.  et al. 2010. Reprogramming of T cells to natural killer–like cells upon Bcl11b deletion. Science 32985–89 [Google Scholar]
9. Kueh HY, Yui MA, Ng KK, Pease SS, Zhang JA. 9.  et al. 2016. Asynchronous combinatorial action of four regulatory factors activates Bcl11b for T cell commitment. Nat. Immunol. 17956–65 [Google Scholar]
10. von Boehmer H Fehling HJ. 10.  1997. Structure and function of the pre-T cell receptor. Annu. Rev. Immunol. 15433–52 [Google Scholar]
11. Yamasaki S, Saito T. 11.  2007. Molecular basis for pre-TCR-mediated autonomous signaling. Trends Immunol 2839–43 [Google Scholar]
12. Krangel MS. 12.  2009. Mechanics of T cell receptor gene rearrangement. Curr. Opin. Immunol. 21133–39 [Google Scholar]
13. Gao GF, Rao Z, Bell JI. 13.  2002. Molecular coordination of αβ T-cell receptors and coreceptors CD8 and CD4 in their recognition of peptide-MHC ligands. Trends Immunol 23408–13 [Google Scholar]
14. Klein L, Kyewski B, Allen PM, Hogquist KA. 14.  2014. Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see). Nat. Rev. Immunol. 14377–91 [Google Scholar]
15. Nitta T, Murata S, Ueno T, Tanaka K, Takahama Y. 15.  2008. Thymic microenvironments for T-cell repertoire formation. Adv. Immunol. 9959–94 [Google Scholar]
16. Cowan JE, Parnell SM, Nakamura K, Caamano JH, Lane PJ. 16.  et al. 2013. The thymic medulla is required for Foxp3⁺ regulatory but not conventional CD4⁺ thymocyte development. J. Exp. Med. 210675–81 [Google Scholar]
17. Ueno T, Saito F, Gray DH, Kuse S, Hieshima K. 17.  et al. 2004. CCR7 signals are essential for cortex-medulla migration of developing thymocytes. J. Exp. Med. 200493–505 [Google Scholar]
18. Brugnera E, Bhandoola A, Cibotti R, Yu Q, Guinter TI. 18.  et al. 2000. Coreceptor reversal in the thymus: signaled CD4⁺8⁺ thymocytes initially terminate CD8 transcription even when differentiating into CD8⁺ T cells. Immunity 1359–71 [Google Scholar]
19. Singer A. 19.  2002. New perspectives on a developmental dilemma: the kinetic signaling model and the importance of signal duration for the CD4/CD8 lineage decision. Curr. Opin. Immunol. 14207–15 [Google Scholar]
20. Singer A, Adoro S, Park JH. 20.  2008. Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice. Nat. Rev. Immunol. 8788–801 [Google Scholar]
21. Germain RN. 21.  2002. T-cell development and the CD4-CD8 lineage decision. Nat. Rev. Immunol. 2309–22 [Google Scholar]
22. Littman DR, Thomas Y, Maddon PJ, Chess L, Axel R. 22.  1985. The isolation and sequence of the gene encoding T8: a molecule defining functional classes of T lymphocytes. Cell 40237–46 [Google Scholar]
23. Maddon PJ, Littman DR, Godfrey M, Maddon DE, Chess L, Axel R. 23.  1985. The isolation and nucleotide sequence of a cDNA encoding the T cell surface protein T4: a new member of the immunoglobulin gene family. Cell 4293–104 [Google Scholar]
24. Chan SH, Cosgrove D, Waltzinger C, Benoist C, Mathis D. 24.  1993. Another view of the selective model of thymocyte selection. Cell 73225–36 [Google Scholar]
25. Davis CB, Killeen N, Crooks ME, Raulet D, Littman DR. 25.  1993. Evidence for a stochastic mechanism in the differentiation of mature subsets of T lymphocytes. Cell 73237–47 [Google Scholar]
26. Robey EA, Fowlkes BJ, Gordon JW, Kioussis D, von Boehmer H. 26.  et al. 1991. Thymic selection in CD8 transgenic mice supports an instructive model for commitment to a CD4 or CD8 lineage. Cell 6499–107 [Google Scholar]
27. Robey E. 27.  1994. Introduction: commitment to CD4 and CD8 lineages—stochastic or instructive?. Semin. Immunol. 6207–8 [Google Scholar]
28. Chan SH, Benoist C, Mathis D. 28.  1994. In favor of the selective model of positive selection. Semin. Immunol. 6241–48 [Google Scholar]
29. Issuree PD, Ng CP, Littman DR. 29.  2017. Heritable gene regulation in the CD4:CD8 T cell lineage choice. Front. Immunol. 8291 [Google Scholar]
30. Cheroutre H, Husain MM. 30.  2013. CD4 CTL: living up to the challenge. Semin. Immunol. 25273–81 [Google Scholar]
31. Veillette A, Zuniga-Pflucker JC, Bolen JB, Kruisbeek AM. 31.  1989. Engagement of CD4 and CD8 expressed on immature thymocytes induces activation of intracellular tyrosine phosphorylation pathways. J. Exp. Med. 1701671–80 [Google Scholar]
32. Wiest DL, Yuan L, Jefferson J, Benveniste P, Tsokos M. 32.  et al. 1993. Regulation of T cell receptor expression in immature CD4⁺CD8⁺ thymocytes by p56lck tyrosine kinase: basis for differential signaling by CD4 and CD8 in immature thymocytes expressing both coreceptor molecules. J. Exp. Med. 1781701–12 [Google Scholar]
33. Hernandez-Hoyos G, Sohn SJ, Rothenberg EV, Alberola-Ila J. 33.  2000. Lck activity controls CD4/CD8 T cell lineage commitment. Immunity 12313–22 [Google Scholar]
34. Bosselut R, Feigenbaum L, Sharrow SO, Singer A. 34.  2001. Strength of signaling by CD4 and CD8 coreceptor tails determines the number but not the lineage direction of positively selected thymocytes. Immunity 14483–94 [Google Scholar]
35. Suzuki H, Punt JA, Granger LG, Singer A. 35.  1995. Asymmetric signaling requirements for thymocyte commitment to the CD4⁺ versus CD8⁺ T cell lineages: a new perspective on thymic commitment and selection. Immunity 2413–25 [Google Scholar]
36. Sarafova SD, Erman B, Yu Q, Van Laethem F, Guinter T. 36.  et al. 2005. Modulation of coreceptor transcription during positive selection dictates lineage fate independently of TCR/coreceptor specificity. Immunity 2375–87 [Google Scholar]
37. Adoro S, McCaughtry T, Erman B, Alag A, Van Laethem F. 37.  et al. 2012. Coreceptor gene imprinting governs thymocyte lineage fate. EMBO J 31366–77 [Google Scholar]
38. Sarafova SD, Van Laethem F, Adoro S, Guinter T, Sharrow SO. 38.  et al. 2009. Upregulation of CD4 expression during MHC class II-specific positive selection is essential for error-free lineage choice. Immunity 31480–90 [Google Scholar]
39. Buenrostro JD, Giresi PG, Zaba LC, Chang HY, Greenleaf WJ. 39.  2013. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 101213–18 [Google Scholar]
40. Sawada S, Littman DR. 40.  1991. Identification and characterization of a T-cell-specific enhancer adjacent to the murine CD4 gene. Mol. Cell. Biol. 115506–15 [Google Scholar]
41. Sawada S, Scarborough JD, Killeen N, Littman DR. 41.  1994. A lineage-specific transcriptional silencer regulates CD4 gene expression during T lymphocyte development. Cell 77917–29 [Google Scholar]
42. Siu G, Wurster AL, Duncan DD, Soliman TM, Hedrick SM. 42.  1994. A transcriptional silencer controls the developmental expression of the CD4 gene. EMBO J 133570–79 [Google Scholar]
43. Zou YR, Sunshine MJ, Taniuchi I, Hatam F, Killeen N, Littman DR. 43.  2001. Epigenetic silencing of CD4 in T cells committed to the cytotoxic lineage. Nat. Genet. 29332–36 [Google Scholar]
44. Leung RK, Thomson K, Gallimore A, Jones E, Van den Broek M. 44.  et al. 2001. Deletion of the CD4 silencer element supports a stochastic mechanism of thymocyte lineage commitment. Nat. Immunol. 21167–73 [Google Scholar]
45. Taniuchi I, Sunshine MJ, Festenstein R, Littman DR. 45.  2002. Evidence for distinct CD4 silencer functions at different stages of thymocyte differentiation. Mol. Cell 101083–96 [Google Scholar]
46. Chong MM, Simpson N, Ciofani M, Chen G, Collins A, Littman DR. 46.  2010. Epigenetic propagation of CD4 expression is established by the Cd4 proximal enhancer in helper T cells. Genes Dev 24659–69 [Google Scholar]
47. Sellars M, Huh JR, Day K, Issuree PD, Galan C. 47.  et al. 2015. Regulation of DNA methylation dictates Cd4 expression during the development of helper and cytotoxic T cell lineages. Nat. Immunol. 16746–54 [Google Scholar]
48. Henson DM, Chou C, Sakurai N, Egawa T. 48.  2014. A silencer-proximal intronic region is required for sustained CD4 expression in postselection thymocytes. J. Immunol. 1924620–27 [Google Scholar]
49. Manjunath N, Shankar P, Stockton B, Dubey PD, Lieberman J, von Andrian UH. 49.  1999. A transgenic mouse model to analyze CD8⁺ effector T cell differentiation in vivo. PNAS 9613932–37 [Google Scholar]
50. Heng TS, Painter MW. 50.  2008. The Immunological Genome Project: networks of gene expression in immune cells. Nat. Immunol. 91091–94 [Google Scholar]
51. Kakugawa K, Kojo S, Tanaka H, Seo W, Endo TA. 51.  et al. 2017. Essential roles of SATB1 in specifying T lymphocyte subsets. Cell Rep 191176–88 [Google Scholar]
52. Sakaguchi S, Hombauer M, Hassan H, Tanaka H, Yasmin N. 52.  et al. 2015. A novel Cd8-cis-regulatory element preferentially directs expression in CD44^hiCD62L⁺ CD8⁺ T cells and in CD8αα⁺ dendritic cells. J. Leukoc. Biol. 97635–44 [Google Scholar]
53. Kioussis D, Ellmeier W. 53.  2002. Chromatin and CD4, CD8A and CD8B gene expression during thymic differentiation. Nat. Rev. Immunol. 2909–19 [Google Scholar]
54. Ellmeier W, Sunshine MJ, Losos K, Littman DR. 54.  1998. Multiple developmental stage-specific enhancers regulate CD8 expression in developing thymocytes and in thymus-independent T cells. Immunity 9485–96 [Google Scholar]
55. Hostert A, Garefalaki A, Mavria G, Tolaini M, Roderick K. 55.  et al. 1998. Hierarchical interactions of control elements determine CD8α gene expression in subsets of thymocytes and peripheral T cells. Immunity 9497–508 [Google Scholar]
56. Ellmeier W, Sunshine MJ, Losos K, Hatam F, Littman DR. 56.  1997. An enhancer that directs lineage-specific expression of CD8 in positively selected thymocytes and mature T cells. Immunity 7537–47 [Google Scholar]
57. Bilic I, Koesters C, Unger B, Sekimata M, Hertweck A. 57.  et al. 2006. Negative regulation of CD8 expression via Cd8 enhancer–mediated recruitment of the zinc finger protein MAZR. Nat. Immunol. 7392–400 [Google Scholar]
58. Carbone AM, Marrack P, Kappler JW. 58.  1988. Demethylated CD8 gene in CD4⁺ T cells suggests that CD4⁺ cells develop from CD8⁺ precursors. Science 2421174–76 [Google Scholar]
59. Harland KL, Day EB, Apte SH, Russ BE, Doherty PC. 59.  et al. 2014. Epigenetic plasticity of Cd8a locus during CD8⁺ T-cell development and effector differentiation and reprogramming. Nat. Commun. 53547 [Google Scholar]
60. Hamerman JA, Page ST, Pullen AM. 60.  1997. Distinct methylation states of the CD8 beta gene in peripheral T cells and intraepithelial lymphocytes. J. Immunol. 1591240–46 [Google Scholar]
61. Lee PP, Fitzpatrick DR, Beard C, Jessup HK, Lehar S. 61.  et al. 2001. A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival. Immunity 15763–74 [Google Scholar]
62. Chi TH, Wan M, Zhao K, Taniuchi I, Chen L. 62.  et al. 2002. Reciprocal regulation of CD4/CD8 expression by SWI/SNF-like BAF complexes. Nature 418195–99 [Google Scholar]
63. Naito T, Gomez-Del Arco P, Williams CJ, Georgopoulos K. 63.  2007. Antagonistic interactions between Ikaros and the chromatin remodeler Mi-2β determine silencer activity and Cd4 gene expression. Immunity 27723–34 [Google Scholar]
64. Taniuchi I, Osato M, Egawa T, Sunshine MJ, Bae SC. 64.  et al. 2002. Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development. Cell 111621–33 [Google Scholar]
65. Muroi S, Naoe Y, Miyamoto C, Akiyama K, Ikawa T. 65.  et al. 2008. Cascading suppression of transcriptional silencers by ThPOK seals helper T cell fate. Nat. Immunol. 91113–21 [Google Scholar]
66. Wildt KF, Sun G, Grueter B, Fischer M, Zamisch M. 66.  et al. 2007. The transcription factor zbtb7b promotes CD4 expression by antagonizing runx-mediated activation of the CD4 silencer. J. Immunol. 1794405–14 [Google Scholar]
67. Yu M, Wan M, Zhang J, Wu J, Khatri R, Chi T. 67.  2008. Nucleoprotein structure of the CD4 locus: implications for the mechanisms underlying CD4 regulation during T cell development. PNAS 1053873–78 [Google Scholar]
68. Speck NA. 68.  2001. Core binding factor and its role in normal hematopoietic development. Curr. Opin. Hematol. 8192–96 [Google Scholar]
69. Levanon D, Groner Y. 69.  2004. Structure and regulated expression of mammalian RUNX genes. Oncogene 234211–19 [Google Scholar]
70. Kagoshima H, Shigesada K, Satake M, Ito Y, Miyoshi H. 70.  et al. 1993. The Runt domain identifies a new family of heteromeric transcriptional regulators. Trends Genet 9338–41 [Google Scholar]
71. Daga A, Tighe JE, Calabi F. 71.  1992. Leukaemia/Drosophila homology. Nature 356484 [Google Scholar]
72. Ito Y. 72.  2008. RUNX genes in development and cancer: regulation of viral gene expression and the discovery of RUNX family genes. Adv. Cancer Res. 9933–76 [Google Scholar]
73. Levanon D, Goldstein RE, Bernstein Y, Tang H, Goldenberg D. 73.  et al. 1998. Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors. PNAS 9511590–95 [Google Scholar]
74. Seo W, Tanaka H, Miyamoto C, Levanon D, Groner Y, Taniuchi I. 74.  2012. Roles of VWRPY motif-mediated gene repression by Runx proteins during T-cell development. Immunol. Cell Biol. 90827–30 [Google Scholar]
75. Yarmus M, Woolf E, Bernstein Y, Fainaru O, Negreanu V. 75.  et al. 2006. Groucho/transducin-like Enhancer-of-split (TLE)-dependent and -independent transcriptional regulation by Runx3. PNAS 1037384–89 [Google Scholar]
76. Egawa T, Tillman RE, Naoe Y, Taniuchi I, Littman DR. 76.  2007. The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells. J. Exp. Med. 2041945–57 [Google Scholar]
77. Kim B, Sasaki Y, Egawa T. 77.  2015. Restriction of nonpermissive RUNX3 protein expression in T lymphocytes by the Kozak sequence. J. Immunol. 1951517–23 [Google Scholar]
78. Spender LC, Whiteman HJ, Karstegl CE, Farrell PJ. 78.  2005. Transcriptional cross-regulation of RUNX1 by RUNX3 in human B cells. Oncogene 241873–81 [Google Scholar]
79. Egawa T, Eberl G, Taniuchi I, Benlagha K, Geissmann F. 79.  et al. 2005. Genetic evidence supporting selection of the Vα14i NKT cell lineage from double-positive thymocyte precursors. Immunity 22705–16 [Google Scholar]
80. Jiang H, Peterlin BM. 80.  2008. Differential chromatin looping regulates CD4 expression in immature thymocytes. Mol. Cell. Biol. 28907–12 [Google Scholar]
81. Hassan H, Sakaguchi S, Tenno M, Kopf A, Boucheron N. 81.  et al. 2011. Cd8 enhancer E8I and Runx factors regulate CD8α expression in activated CD8⁺ T cells. PNAS 10818330–35 [Google Scholar]
82. Pobezinsky LA, Angelov GS, Tai X, Jeurling S, Van Laethem F. 82.  et al. 2012. Clonal deletion and the fate of autoreactive thymocytes that survive negative selection. Nat. Immunol. 13569–78 [Google Scholar]
83. Sato T, Ohno S, Hayashi T, Sato C, Kohu K. 83.  et al. 2005. Dual functions of Runx proteins for reactivating CD8 and silencing CD4 at the commitment process into CD8 thymocytes. Immunity 22317–28 [Google Scholar]
84. He X, Dave VP, Zhang Y, Hua X, Nicolas E. 84.  et al. 2005. The zinc finger transcription factor Th-POK regulates CD4 versus CD8 T-cell lineage commitment. Nature 433826–33 [Google Scholar]
85. Dave VP, Allman D, Keefe R, Hardy RR, Kappes DJ. 85.  1998. HD mice: a novel mouse mutant with a specific defect in the generation of CD4⁺ T cells. PNAS 958187–92 [Google Scholar]
86. Sun G, Liu X, Mercado P, Jenkinson SR, Kypriotou M. 86.  et al. 2005. The zinc finger protein cKrox directs CD4 lineage differentiation during intrathymic T cell positive selection. Nat. Immunol. 6373–81 [Google Scholar]
87. Keefe R, Dave V, Allman D, Wiest D, Kappes DJ. 87.  1999. Regulation of lineage commitment distinct from positive selection. Science 2861149–53 [Google Scholar]
88. Kappes DJ, He X. 88.  2006. Role of the transcription factor Th-POK in CD4:CD8 lineage commitment. Immunol. Rev. 209237–52 [Google Scholar]
89. Harker N, Naito T, Cortes M, Hostert A, Hirschberg S. 89.  et al. 2002. The CD8α gene locus is regulated by the Ikaros family of proteins. Mol. Cell 101403–15 [Google Scholar]
90. Sridharan R, Smale ST. 90.  2007. Predominant interaction of both Ikaros and Helios with the NuRD complex in immature thymocytes. J. Biol. Chem. 28230227–38 [Google Scholar]
91. Banan M, Rojas IC, Lee WH, King HL, Harriss JV. 91.  et al. 1997. Interaction of the nuclear matrix-associated region (MAR)-binding proteins, SATB1 and CDP/Cux, with a MAR element (L2a) in an upstream regulatory region of the mouse CD8a gene. J. Biol. Chem. 27218440–52 [Google Scholar]
92. Yao X, Nie H, Rojas IC, Harriss JV, Maika SD. 92.  et al. 2010. The L2a element is a mouse CD8 silencer that interacts with MAR-binding proteins SATB1 and CDP. Mol. Immunol. 48153–63 [Google Scholar]
93. Kitagawa Y, Ohkura N, Kidani Y, Vandenbon A, Hirota K. 93.  et al. 2017. Guidance of regulatory T cell development by Satb1-dependent super-enhancer establishment. Nat. Immunol. 18173–83 [Google Scholar]
94. Aliahmad P, Kaye J. 94.  2008. Development of all CD4 T lineages requires nuclear factor TOX. J. Exp. Med. 205245–56 [Google Scholar]
95. Seehus CR, Aliahmad P, de la Torre B, Iliev ID, Spurka L. 95.  et al. 2015. The development of innate lymphoid cells requires TOX-dependent generation of a common innate lymphoid cell progenitor. Nat. Immunol. 16599–608 [Google Scholar]
96. He X, Park K, Wang H, He X, Zhang Y. 96.  et al. 2008. CD4-CD8 lineage commitment is regulated by a silencer element at the ThPOK transcription-factor locus. Immunity 28346–58 [Google Scholar]
97. Muroi S, Tanaka H, Miyamoto C, Taniuchi I. 97.  2013. Cutting edge: fine-tuning of Thpok gene activation by an enhancer in close proximity to its own silencer. J. Immunol. 1901397–401 [Google Scholar]
98. Setoguchi R, Tachibana M, Naoe Y, Muroi S, Akiyama K. 98.  et al. 2008. Repression of the transcription factor Th-POK by Runx complexes in cytotoxic T cell development. Science 319822–25 [Google Scholar]
99. Hedrick SM. 99.  2008. Thymus lineage commitment: a single switch. Immunity 28297–99 [Google Scholar]
100. Tanaka H, Naito T, Muroi S, Seo W, Chihara R. 100.  et al. 2013. Epigenetic Thpok silencing limits the time window to choose CD4⁺ helper-lineage fate in the thymus. EMBO J 321183–94 [Google Scholar]
101. Durst KL, Hiebert SW. 101.  2004. Role of RUNX family members in transcriptional repression and gene silencing. Oncogene 234220–24 [Google Scholar]
102. Egawa T, Littman DR. 102.  2008. ThPOK acts late in specification of the helper T cell lineage and suppresses Runx-mediated commitment to the cytotoxic T cell lineage. Nat. Immunol. 91131–39 [Google Scholar]
103. Wang L, Wildt KF, Castro E, Xiong Y, Feigenbaum L. 103.  et al. 2008. The zinc finger transcription factor Zbtb7b represses CD8-lineage gene expression in peripheral CD4⁺ T cells. Immunity 29876–87 [Google Scholar]
104. Taniuchi I. 104.  2009. Transcriptional regulation in helper versus cytotoxic-lineage decision. Curr. Opin. Immunol. 21127–32 [Google Scholar]
105. Kojo S, Tanaka H, Endo TA, Muroi S, Liu Y. 105.  et al. 2017. Priming of lineage-specifying genes by Bcl11b is required for lineage choice in post-selection thymocytes. Nat. Commun 8702 [Google Scholar]
106. Sakaguchi S, Hombauer M, Bilic I, Naoe Y, Schebesta A. 106.  et al. 2010. The zinc-finger protein MAZR is part of the transcription factor network that controls the CD4 versus CD8 lineage fate of double-positive thymocytes. Nat. Immunol. 11442–48 [Google Scholar]
107. Sakaguchi S, Hainberger D, Tizian C, Tanaka H, Okuda T. 107.  et al. 2015. MAZR and Runx factors synergistically repress ThPOK during CD8⁺ T cell lineage development. J. Immunol. 1952879–87 [Google Scholar]
108. Avram D, Califano D. 108.  2014. The multifaceted roles of Bcl11b in thymic and peripheral T cells: impact on immune diseases. J. Immunol. 1932059–65 [Google Scholar]
109. VanValkenburgh J, Albu DI, Bapanpally C, Casanova S, Califano D. 109.  et al. 2011. Critical role of Bcl11b in suppressor function of T regulatory cells and prevention of inflammatory bowel disease. J. Exp. Med. 2082069–81 [Google Scholar]
110. Albu DI, VanValkenburgh J, Morin N, Califano D, Jenkins NA. 110.  et al. 2011. Transcription factor Bcl11b controls selection of invariant natural killer T-cells by regulating glycolipid presentation in double-positive thymocytes. PNAS 1086211–16 [Google Scholar]
111. Walker JA, Oliphant CJ, Englezakis A, Yu Y, Clare S. 111.  et al. 2015. Bcl11b is essential for group 2 innate lymphoid cell development. J. Exp. Med. 212875–82 [Google Scholar]
112. Yu Y, Wang C, Clare S, Wang J, Lee SC. 112.  et al. 2015. The transcription factor Bcl11b is specifically expressed in group 2 innate lymphoid cells and is essential for their development. J. Exp. Med. 212865–74 [Google Scholar]
113. Califano D, Cho JJ, Uddin MN, Lorentsen KJ, Yang Q. 113.  et al. 2015. Transcription factor Bcl11b controls identity and function of mature type 2 innate lymphoid cells. Immunity 43354–68 [Google Scholar]
114. Kastner P, Chan S, Vogel WK, Zhang LJ, Topark-Ngarm A. 114.  et al. 2010. Bcl11b represses a mature T-cell gene expression program in immature CD4⁺CD8⁺ thymocytes. Eur. J. Immunol. 402143–54 [Google Scholar]
115. Albu DI, Feng D, Bhattacharya D, Jenkins NA, Copeland NG. 115.  et al. 2007. BCL11B is required for positive selection and survival of double-positive thymocytes. J. Exp. Med. 2043003–15 [Google Scholar]
116. Cai S, Lee CC, Kohwi-Shigematsu T. 116.  2006. SATB1 packages densely looped, transcriptionally active chromatin for coordinated expression of cytokine genes. Nat. Genet. 381278–88 [Google Scholar]
117. Xu J, Sankaran VG, Ni M, Menne TF, Puram RV. 117.  et al. 2010. Transcriptional silencing of γ-globin by BCL11A involves long-range interactions and cooperation with SOX6. Genes Dev 24783–98 [Google Scholar]
118. Wang L, Wildt KF, Zhu J, Zhang X, Feigenbaum L. 118.  et al. 2008. Distinct functions for the transcription factors GATA-3 and ThPOK during intrathymic differentiation of CD4⁺ T cells. Nat. Immunol. 91122–30 [Google Scholar]
119. Hosoya T, Maillard I, Engel JD. 119.  2010. From the cradle to the grave: activities of GATA-3 throughout T-cell development and differentiation. Immunol. Rev. 238110–25 [Google Scholar]
120. Hernandez-Hoyos G, Anderson MK, Wang C, Rothenberg EV, Alberola-Ila J. 120.  2003. GATA-3 expression is controlled by TCR signals and regulates CD4/CD8 differentiation. Immunity 1983–94 [Google Scholar]
121. Pai SY, Truitt ML, Ting CN, Leiden JM, Glimcher LH, Ho IC. 121.  2003. Critical roles for transcription factor GATA-3 in thymocyte development. Immunity 19863–75 [Google Scholar]
122. Steinke FC, Yu S, Zhou X, He B, Yang W. 122.  et al. 2014. TCF-1 and LEF-1 act upstream of Th-POK to promote the CD4⁺ T cell fate and interact with Runx3 to silence Cd4 in CD8⁺ T cells. Nat. Immunol. 15646–56 [Google Scholar]
123. Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H. 123.  et al. 2009. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324930–35 [Google Scholar]
124. Kriaucionis S, Heintz N. 124.  2009. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science 324929–30 [Google Scholar]
125. Ito S, Shen L, Dai Q, Wu SC, Collins LB. 125.  et al. 2011. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 3331300–3 [Google Scholar]
126. Tsagaratou A, Gonzalez-Avalos E, Rautio S, Scott-Browne JP, Togher S. 126.  et al. 2017. TET proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells. Nat. Immunol. 1845–53 [Google Scholar]
127. Appel E, Weissmann S, Salzberg Y, Orlovsky K, Negreanu V. 127.  et al. 2016. An ensemble of regulatory elements controls Runx3 spatiotemporal expression in subsets of dorsal root ganglia proprioceptive neurons. Genes Dev 302607–22 [Google Scholar]
128. Park JH, Adoro S, Guinter T, Erman B, Alag AS. 128.  et al. 2010. Signaling by intrathymic cytokines, not T cell antigen receptors, specifies CD8 lineage choice and promotes the differentiation of cytotoxic-lineage T cells. Nat. Immunol. 11257–64 [Google Scholar]
129. McCaughtry TM, Etzensperger R, Alag A, Tai X, Kurtulus S. 129.  et al. 2012. Conditional deletion of cytokine receptor chains reveals that IL-7 and IL-15 specify CD8 cytotoxic lineage fate in the thymus. J. Exp. Med. 2092263–76 [Google Scholar]
130. Luckey MA, Kimura MY, Waickman AT, Feigenbaum L, Singer A, Park JH. 130.  2014. The transcription factor ThPOK suppresses Runx3 and imposes CD4⁺ lineage fate by inducing the SOCS suppressors of cytokine signaling. Nat. Immunol. 15638–45 [Google Scholar]
131. Leonard WJ. 131.  2001. Role of Jak kinases and STATs in cytokine signal transduction. Int. J. Hematol. 73271–77 [Google Scholar]
132. Xiong Y, Castro E, Yagi R, Zhu J, Lesourne R. 132.  et al. 2013. Thpok-independent repression of Runx3 by Gata3 during CD4⁺ T-cell differentiation in the thymus. Eur. J. Immunol. 43918–28 [Google Scholar]
133. Rodriguez RM, Lopez-Larrea C, Suarez-Alvarez B. 133.  2015. Epigenetic dynamics during CD4⁺ T cells lineage commitment. Int. J. Biochem. Cell Biol. 6775–85 [Google Scholar]
134. Konkel JE, Maruyama T, Carpenter AC, Xiong Y, Zamarron BF. 134.  et al. 2011. Control of the development of CD8αα⁺ intestinal intraepithelial lymphocytes by TGF-β. Nat. Immunol. 12312–19 [Google Scholar]
135. Naoe Y, Setoguchi R, Akiyama K, Muroi S, Kuroda M. 135.  et al. 2007. Repression of interleukin-4 in T helper type 1 cells by Runx/Cbfβ binding to the Il4 silencer. J. Exp. Med. 2041749–55 [Google Scholar]
136. Djuretic IM, Levanon D, Negreanu V, Groner Y, Rao A, Ansel KM. 136.  2007. Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells. Nat. Immunol. 8145–53 [Google Scholar]
137. Mucida D, Husain MM, Muroi S, van Wijk F, Shinnakasu R. 137.  et al. 2013. Transcriptional reprogramming of mature CD4⁺ helper T cells generates distinct MHC class II–restricted cytotoxic T lymphocytes. Nat. Immunol. 14281–89 [Google Scholar]
138. Takeuchi A, Badr Mel S, Miyauchi K, Ishihara C, Onishi R. 138.  et al. 2016. CRTAM determines the CD4⁺ cytotoxic T lymphocyte lineage. J. Exp. Med. 213123–38 [Google Scholar]
139. Nakayamada S, Takahashi H, Kanno Y, O'Shea JJ. 139.  2012. Helper T cell diversity and plasticity. Curr. Opin. Immunol. 24297–302 [Google Scholar]
140. Appay V, Zaunders JJ, Papagno L, Sutton J, Jaramillo A. 140.  et al. 2002. Characterization of CD4⁺ CTLs ex vivo. J. Immunol. 1685954–58 [Google Scholar]
141. Brown DM. 141.  2010. Cytolytic CD4 cells: Direct mediators in infectious disease and malignancy. Cell Immunol 26289–95 [Google Scholar]
142. Marshall NB, Swain SL. 142.  2011. Cytotoxic CD4 T cells in antiviral immunity. J. Biomed. Biotechnol. 2011954602 [Google Scholar]
143. Reis BS, Hoytema van Konijnenburg DP, Grivennikov SI, Mucida D. 143.  2014. Transcription factor T-bet regulates intraepithelial lymphocyte functional maturation. Immunity 41244–56 [Google Scholar]
144. Reis B, Rogoz A, Costa-Pinto F, Taniuchi I, Mucida D. 144.  2013. Mutual expression of the transcription factors Runx3 and ThPOK regulates intestinal CD4⁺ T cell immunity. Nat. Immunol. 14271–80 [Google Scholar]
145. Sujino T, London M, Hoytema van Konijnenburg DP, Rendon T, Buch T. 145.  et al. 2016. Tissue adaptation of regulatory and intraepithelial CD4⁺ T cells controls gut inflammation. Science 3521581–86 [Google Scholar]
146. Vogel WK, Gafken PR, Leid M, Filtz TM. 146.  2014. Kinetic analysis of BCL11B multisite phosphorylation–dephosphorylation and coupled sumoylation in primary thymocytes by multiple reaction monitoring mass spectroscopy. J. Proteome Res. 135860–68 [Google Scholar]
147. Zheng Y, Josefowicz S, Chaudhry A, Peng XP, Forbush K, Rudensky AY. 147.  2010. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature 463808–12 [Google Scholar]
148. Feng Y, van der Veeken J, Shugay M, Putintseva EV, Osmanbeyoglu HU. 148.  et al. 2015. A mechanism for expansion of regulatory T-cell repertoire and its role in self-tolerance. Nature 528132–36 [Google Scholar]
149. Star B, Nederbragt AJ, Jentoft S, Grimholt U, Malmstrom M. 149.  et al. 2011. The genome sequence of Atlantic cod reveals a unique immune system. Nature 477207–10 [Google Scholar]
150. Venkatesh B, Lee AP, Ravi V, Maurya AK, Lian MM. 150.  et al. 2014. Elephant shark genome provides unique insights into gnathostome evolution. Nature 505174–79 [Google Scholar]
151. Laing KJ, Zou JJ, Purcell MK, Phillips R, Secombes CJ, Hansen JD. 151.  2006. Evolution of the CD4 family: teleost fish possess two divergent forms of CD4 in addition to lymphocyte activation gene-3. J. Immunol. 1773939–51 [Google Scholar]
152. Takizawa F, Magadan S, Parra D, Xu Z, Korytar T. 152.  et al. 2016. Novel teleost CD4-bearing cell populations provide insights into the evolutionary origins and primordial roles of CD4⁺ lymphocytes and CD4⁺ macrophages. J. Immunol. 1964522–35 [Google Scholar]