CD4 +T cells: Differentiation and functions

Clinical and Developmental Immunology

Volumn 2012, Issue , 2012, Pages

  Luckheeram, Rishi Vishal ^a   Zhou, Rui ^a,b   Verma, Asha Devi ^c   Xia, Bing ^a,b,d  

^a WUHAN UNIVERSITY   (China)

^b WUHAN UNIVERSITY   (China)

^c RENMIN HOSPITAL OF WUHAN UNIVERSITY   (China)

^d Clinical Centre of Intestinal and Colorectal Diseases   (China)

Author keywords

[No Author keywords available]

Indexed keywords

AROMATIC HYDROCARBON RECEPTOR; EOMESODERMIN; GAMMA INTERFERON; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 21; INTERLEUKIN 23; INTERLEUKIN 27; INTERLEUKIN 4; INTERLEUKIN 6; RETINOID RELATED ORPHAN RECEPTOR ALPHA; SMAD2 PROTEIN; SMAD3 PROTEIN; STAT1 PROTEIN; STAT4 PROTEIN; STAT5 PROTEIN; T BOX TRANSCRIPTION FACTOR; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR FOXP3; TRANSCRIPTION FACTOR GATA 3; TRANSCRIPTION FACTOR RUNX1; TRANSCRIPTION FACTOR RUNX3; TRANSFORMING GROWTH FACTOR BETA; CYTOKINE; TRANSCRIPTION FACTOR;

CD4+ T LYMPHOCYTE; CELL FUNCTION; CELL SELECTION; CYTOKINE PRODUCTION; DENDRITIC CELL; GENE DELETION; GENE INSERTION; GENE REARRANGEMENT; HELPER CELL; LYMPHOCYTE DIFFERENTIATION; LYMPHOPOIESIS; NATURAL KILLER CELL; NONHUMAN; PLASTICITY; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; T LYMPHOCYTE ACTIVATION; TH1 CELL; TH17 CELL; TH2 CELL; THYMOCYTE; ANIMAL; BIOSYNTHESIS; CELL DIFFERENTIATION; CYTOLOGY; GENE EXPRESSION REGULATION; GENETIC EPIGENESIS; GENETICS; HUMAN; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; MOUSE; SIGNAL TRANSDUCTION;

ANIMALS; CELL DIFFERENTIATION; CYTOKINES; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION; HUMANS; LYMPHOCYTE ACTIVATION; MICE; SIGNAL TRANSDUCTION; T-LYMPHOCYTES, REGULATORY; TH1 CELLS; TH17 CELLS; TH2 CELLS; TRANSCRIPTION FACTORS;

EID: 84859709877     PISSN: 17402522     EISSN: 17402530     Source Type: Journal    
DOI: 10.1155/2012/925135     Document Type: Review

References (151)

1. Klein L., Hinterberger M., Wirnsberger G., Kyewski B., Antigen presentation in the thymus for positive selection and central tolerance induction Nature Reviews Immunology 2009 9 12 833 844
2. Gill J., Malin M., Sutherland J., Gray D., Hollander G., Boyd R., Thymic generation and regeneration Immunological Reviews 2003 195 28 50 (Pubitemid 37153451)
3. Takahama Y., Journey through the thymus: stromal guides for T-cell development and selection Nature Reviews Immunology 2006 6 2 127 135 (Pubitemid 43361588)
4. Daniels M. A., Teixeiro E., Gill J., Hausmann B., Roubaty D., Holmberg K., Werlen G., Hollnder G. A., Gascoigne N. R. J., Palmer E., Thymic selection threshold defined by compartmentalization of Ras/MAPK signalling Nature 2006 444 7120 724 729 (Pubitemid 44949596)
5. Rudolph M. G., Stanfield R. L., Wilson I. A., How TCRs bind MHCs, peptides, and coreceptors Annual Review of Immunology 2006 24 419 466
6. Starr T. K., Jameson S. C., Hogquist K. A., Positive and negative selection of T cells Annual Review of Immunology 2003 21 139 176 (Pubitemid 37174529)
7. Cabaniols J. P., Fazilleau N., Casrouge A., Kourilsky P., Kanellopoulos J. M., Most / T cell receptor diversity is due to terminal deoxynucleotidyl transferase Journal of Experimental Medicine 2001 194 9 1385 1390 (Pubitemid 33055055)
8. Rock E. P., Sibbald P. R., Davis M. M., Chien Y. H., CDR3 length in antigen-specific immune receptors Journal of Experimental Medicine 1994 179 1 323 328 (Pubitemid 24012999)
9. Treiner E., Lantz O., CD1d- and MR1-restricted invariant T cells: of mice and men Current Opinion in Immunology 2006 18 5 519 526 (Pubitemid 44311447)
10. Drayton D. L., Liao S., Mounzer R. H., Ruddle N. H., Lymphoid organ development: from ontogeny to neogenesis Nature Immunology 2006 7 4 344 353
11. Ashkar S., Weber G. F., Panoutsakopoulou V., Sanchirico M. E., Jansson M., Zawaideh S., Rittling S. R., Denhardt D. T., Glimcher M. J., Cantor H., Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity Science 2000 287 5454 860 864 (Pubitemid 30084330)
12. Tao X., Constant S., Jorritsma P., Bottomly K., Strength of TCR Signal Determines the Costimulatory Requirements for Th1 and Th2 CD4+ T Cell Differentiation Journal of Immunology 1997 159 12 5956 5963 (Pubitemid 127471531)
13. Jenkins M. K., Khoruts A., Ingulli E., Mueller D. L., McSorley S. J., Lee Reinhardt R., Itano A., Pape K. A., In vivo activation of antigen-specific CD4 T cells Annual Review of Immunology 2001 19 23 45 (Pubitemid 32368028)
14. Steinman R. M., Hawiger D., Nussenzweig M. C., Tolerogenic dendritic cells Annual Review of Immunology 2003 21 685 711 (Pubitemid 37174545)
15. Iwasaki A., Medzhitov R., Toll-like receptor control of the adaptive immune responses Nature Immunology 2004 5 10 987 995 (Pubitemid 41057715)
16. Kohu K., Ohmori H., Wong W. F., Onda D., Wakoh T., Kon S., Yamashita M., Nakayama T., Kubo M., Satake M., The Runx3 transcription factor augments Th1 and down-modulates Th2 Phenotypes by interacting with and attenuating GATA3 Journal of Immunology 2009 183 12 7817 7824
17. Greenwald R. J., Freeman G. J., Sharpe A. H., The B7 family revisited Annual Review of Immunology 2005 23 515 548 (Pubitemid 40563179)
18. Croft M., The role of TNF superfamily members in T-cell function and diseases Nature Reviews Immunology 2009 9 4 271 285
19. Trinchieri G., Pflanz S., Kastelein R. A., The IL-12 family of heterodimeric cytokines: new players in the regulation of T cell responses Immunity 2003 19 5 641 644 (Pubitemid 37490789)
20. Trinchieri G., Sher A., Cooperation of Toll-like receptor signals in innate immune defence Nature Reviews Immunology 2007 7 3 179 190
21. Afkarian M., Sedy J. R., Yang J., Jacobson N. G., Cereb N., Yang S. Y., Murphy T. L., Murphy K. M., T-bet is a STATI-induced regulator for IL-12R expression in nave CD4 + T cells Nature Immunology 2002 3 6 549 557 (Pubitemid 34662307)
22. Lugo-Villarino G., Maldonado-Lpez R., Possemato R., Pearanda C., Glimcher L. H., T-bet is required for optimal production of IFN- and antigen-specific T cell activation by dendritic cells Proceedings of the National Academy of Sciences of the United States of America 2003 100 13 7749 7754 (Pubitemid 36760041)
23. Lazarevic V., Chen X., Shim J. H., Hwang E. S., Jang E., Bolm A. N., Oukka M., Kuchroo V. K., Glimcher L. H., T-bet represses TH 17 differentiation by preventing Runx1-mediated activation of the gene encoding ROR t Nature Immunology 2011 12 1 96 104
24. Lighvani A. A., Frucht D. M., Jankovic D., Yamane H., Aliberti J., Hissong B. D., Nguyen B. V., Gadina M., Sher A., Paul W. E., O'Shea J. J., T-bet is rapidly induced by interferon- in lymphoid and myeloid cells Proceedings of the National Academy of Sciences of the United States of America 2001 98 26 15137 15142 (Pubitemid 34013982)
25. Djuretic I. M., Levanon D., Negreanu V., Groner Y., Rao A., Ansel K. M., Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells Nature Immunology 2007 8 2 145 153 (Pubitemid 46152645)
26. Hwang E. S., Szabo S. J., Schwartzberg P. L., Glimcher L. H., T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3 Science 2005 307 5708 430 433 (Pubitemid 40139989)
27. Thierfelder W. E., Van Deursen J. M., Yamamoto K., Tripp R. A., Sarawar S. R., Carson R. T., Sangster M. Y., Vignali D. A. A., Doherty P. C., Grosveld G. C., Ihle J. N., Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells Nature 1996 382 6587 171 174 (Pubitemid 26242884)
28. Aune T. M., Collins P. L., Chang S., Epigenetics and T helper 1 differentiation Immunology 2009 126 3 299 305
29. Thieu V. T., Yu Q., Chang H. C., Yeh N., Nguyen E. T., Sehra S., Kaplan M. H., Signal transducer and activator of transcription 4 is required for the transcription factor T-bet to promote T helper 1 cell-fate determination Immunity 2008 29 5 679 690
30. Komine O., Hayashi K., Natsume W., Watanabe T., Seki Y., Seki N., Yagi R., Sukzuki W., Tamauchi H., Hozumi K., Habu S., Kubo M., Satake M., The Runx1 transcription factor inhibits the differentiation of naive CD4 + T cells into the Th2 lineage by repressing GATA3 expression Journal of Experimental Medicine 2003 198 1 51 61 (Pubitemid 36870185)
31. Oestreich K. J., Huang A. C., Weinmann A. S., The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns Journal of Experimental Medicine 2011 208 5 1001 1013
32. Fujio K., Okamura T., Yamamoto K., The family of IL-10-secreting CD4+ T cells Advances in Immunology 2010 105 C 99 130
33. Mullen A. C., Hutchins A. S., High F. A., Lee H. W., Sykes K. J., Chodosh L. A., Reiner S. L., Hlx is induced by and genetically interacts with T-bet to promote heritable THI gene induction Nature Immunology 2002 3 7 652 658 (Pubitemid 34752474)
34. Kaplan M. H., Schindler U., Smiley S. T., Grusby M. J., Stat6 is required for mediating responses to IL-4 and for the development of Th2 cells Immunity 1996 4 3 313 319 (Pubitemid 26132509)
35. Glimcher L. H., Murphy K. M., Lineage commitment in the immune system: the T helper lymphocyte grows up Genes and Development 2000 14 14 1693 1711 (Pubitemid 30602989)
36. Zhu J., Guo L., Watson C. J., Hu-Li J., Paul W. E., Stat6 is necessary and sufficient for IL-4's role in TH2 differentiation and cell expansion Journal of Immunology 2001 166 12 7276 7281 (Pubitemid 32525602)
37. Zhu J., Yamane H., Cote-Sierra J., Guo L., Paul W. E., GATA-3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cell-specific factors Cell Research 2006 16 1 3 10 (Pubitemid 43129303)
38. Usui T., Nishikomori R., Kitani A., Strober W., GATA-3 suppresses Th1 development by downregulation of Stat4 and not through effects on IL-12R 2 chain or T-bet Immunity 2003 18 3 415 428 (Pubitemid 36351520)
39. Zhu J., Min B., Hu-Li J., Watson C. J., Grinberg A., Wang Q., Killeen N., Urban J. F., Guo L., Paul W. E., Conditional deletion of Gata3 shows its essential function in TH1-TH2 responses Nature Immunology 2004 5 11 1157 1165 (Pubitemid 39549630)
40. Pai S. Y., Truitt M. L., Ho I. C., GATA-3 deficiency abrogates the development and maintenance of T helper type 2 cells Proceedings of the National Academy of Sciences of the United States of America 2004 101 7 1993 1998 (Pubitemid 38229003)
41. Horiuchi S., Onodera A., Hosokawa H., Watanabe Y., Tanaka T., Sugano S., Suzuki Y., Nakayama T., Genome-wide analysis reveals unique regulation of transcription of Th2-specific genes by GATA3 Journal of Immunology 2011 186 11 6378 6389
42. Boehm U., Klamp T., Groot M., Howard J. C., Cellular responses to interferon- Annual Review of Immunology 1997 15 749 795
43. Halonen S. K., Taylor G. A., Weiss L. M., Gamma interferon-induced inhibition of Toxoplasma gondii in astrocytes is mediated by IGTP Infection and Immunity 2001 69 9 5573 5576 (Pubitemid 32786493)
44. Cote-Sierra J., Foucras G., Guo L., Chiodetti L., Young H. A., Hu-Li J., Zhu J., Paul W. E., Interleukin 2 plays a central role in Th2 differentiation Proceedings of the National Academy of Sciences of the United States of America 2004 101 11 3880 3885 (Pubitemid 38381071)
45. Zhu J., Cote-Sierra J., Guo L., Paul W. E., Stat5 activation plays a critical role in Th2 differentiation Immunity 2003 19 5 739 748 (Pubitemid 37490798)
46. Kim J. I., Ho I. C., Grusby M. J., Glimcher L. H., The transcription factor c-Maf controls the production of interleukin-4 but not other Th2 cytokines Immunity 1999 10 6 745 751 (Pubitemid 29302927)
47. Stritesky G. L., Muthukrishnan R., Sehra S., Goswami R., Pham D., Travers J., Nguyen E. T., Levy D. E., Kaplan M. H., The transcription factor STAT3 is required for T helper 2 cell development Immunity 2011 34 1 39 49
48. Stritesky G. L., Kaplan M. H., Changing the STATus quo in T helper cells Transcription 2011 2 4 179 182
49. Diehl S., Rincn M., The two faces of IL-6 on Th1/Th2 differentiation Molecular Immunology 2002 39 9 531 536 (Pubitemid 35341492)
50. Diehl S., Anguita J., Hoffmeyer A., Zapton T., Ihle J. N., Fikrig E., Rincn M., Inhibition of Th1 differentiation by IL-6 is mediated by SOCS1 Immunity 2000 13 6 805 815 (Pubitemid 32041803)
51. Zhu J., Jankovic D., Grinberg A., Guo L., Paul W. E., Gfi-1 plays an important role in IL-2-mediated Th2 cell expansion Proceedings of the National Academy of Sciences of the United States of America 2006 103 48 18214 18219 (Pubitemid 44871638)
52. Zhu J., Guo L., Min B., Watson C. J., Hu-Li J., Young H. A., Tsichlis P. N., Paul W. E., Growth factor independent-1 induced by IL-4 regulates Th2 cell proliferation Immunity 2002 16 5 733 744 (Pubitemid 34626693)
53. Ho I. C., Lo D., Glimcher L. H., c-maf Promotes T helper cell type 2 (Th2) and attenuates Th1 differentiation by both interleukin 4-dependent and -independent mechanisms Journal of Experimental Medicine 1998 188 10 1859 1866 (Pubitemid 28536773)
54. Rengarajan J., Mowen K. A., McBride K. D., Smith E. D., Singh H., Glimcher L. H., Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression Journal of Experimental Medicine 2002 195 8 1003 1012 (Pubitemid 34412002)
55. Lohoff M., Mittrcker H. W., Prechtl S., Bischof S., Sommer F., Kock S., Ferrick D. A., Duncan G. S., Gessner A., Mak T. W., Dysregulated T helper cell differentiation in the absence of interferon regulatory factor 4 Proceedings of the National Academy of Sciences of the United States of America 2002 99 18 11808 11812 (Pubitemid 34994480)
56. Veldhoen M., Uyttenhove C., van Snick J., Helmby H., Westendorf A., Buer J., Martin B., Wilhelm C., Stockinger B., Transforming growth factor- reprograms the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset Nature Immunology 2008 9 12 1341 1346
57. Staudt V., Bothur E., Klein M., Lingnau K., Reuter S., Grebe N., Gerlitzki B., Hoffmann M., Ulges A., Taube C., Dehzad N., Becker M., Stassen M., Steinborn A., Lohoff M., Schild H., Schmitt E., Bopp T., Interferon-regulatory factor 4 is essential for the developmental program of T helper 9 cells Immunity 2010 33 2 192 202
58. Veldhoen M., Hocking R. J., Atkins C. J., Locksley R. M., Stockinger B., TGF in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells Immunity 2006 24 2 179 189 (Pubitemid 43214587)
59. Mangan P. R., Harrington L. E., O'Quinn D. B., Helms W. S., Bullard D. C., Elson C. O., Hatton R. D., Wahl S. M., Schoeb T. R., Weaver C. T., Transforming growth factor- induces development of the T H17 lineage Nature 2006 441 7090 231 234
60. Bettelli E., Carrier Y., Gao W., Korn T., Strom T. B., Oukka M., Weiner H. L., Kuchroo V. K., Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells Nature 2006 441 7090 235 238
61. Manel N., Unutmaz D., Littman D. R., The differentiation of human TH-17 cells requires transforming growth factor- and induction of the nuclear receptor ROR t Nature Immunology 2008 9 6 641 649 (Pubitemid 351714729)
62. Volpe E., Servant N., Zollinger R., Bogiatzi S. I., Hupé P., Barillot E., Soumelis V., A critical function for transforming growth factor-, interleukin 23 and proinflammatory cytokines in driving and modulating human TH-17 responses Nature Immunology 2008 9 6 650 657 (Pubitemid 351712635)
63. Chen W., Jin W., Hardegen N., Lei K. J., Li L., Marinos N., McGrady G., Wahl S. M., Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF- induction of transcription factor foxp3 Journal of Experimental Medicine 2003 198 12 1875 1886 (Pubitemid 38032120)
64. Zhou L., Lopes J. E., Chong M. M. W., Ivanov I. I., Min R., Victora G. D., Shen Y., Du J., Rubtsov Y. P., Rudensky A. Y., Ziegler S. F., Littman D. R., TGF- -induced Foxp3 inhibits TH17 cell differentiation by antagonizing ROR t function Nature 2008 453 7192 236 240 (Pubitemid 351667978)
65. Qin H., Wang L., Feng T., Elson C. O., Niyongere S. A., Lee S. J., Reynolds S. L., Weaver C. T., Roarty K., Serra R., Benveniste E. N., Cong Y., TGF- promotes Th17 cell development through inhibition of SOCS3 Journal of Immunology 2009 183 1 97 105
66. Ivanov I. I., McKenzie B. S., Zhou L., Tadokoro C. E., Lepelley A., Lafaille J. J., Cua D. J., Littman D. R., The orphan nuclear receptor ROR t directs the differentiation program of proinflammatory IL-17+ T helper cells Cell 2006 126 6 1121 1133 (Pubitemid 44380299)
67. Yang X. O., Pappu B. P., Nurieva R., Akimzhanov A., Kang H. S., Chung Y., Ma L., Shah B., Panopoulos A. D., Schluns K. S., Watowich S. S., Tian Q., Jetten A. M., Dong C., T Helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR and ROR Immunity 2008 28 1 29 39
68. Yang X. O., Panopoulos A. D., Nurieva R., Seon H. C., Wang D., Watowich S. S., Dong C., STAT3 regulates cytokine-mediated generation of inflammatory helper T cells Journal of Biological Chemistry 2007 282 13 9358 9363 (Pubitemid 47104613)
69. Chen Z., Laurence A., Kanno Y., Pacher-Zavisin M., Zhu B. M., Tato C., Yoshimura A., Hennighausen L., O'Shea J. J., Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells Proceedings of the National Academy of Sciences of the United States of America 2006 103 21 8137 8142 (Pubitemid 43801065)
70. Zhang F., Meng G., Strober W., Interactions among the transcription factors Runx1, ROR t and Foxp3 regulate the differentiation of interleukin 17-producing T cells Nature Immunology 2008 9 11 1297 1306
71. Lazarevic V., Chen X., Shim J. H., Hwang E. S., Jang E., Bolm A. N., Oukka M., Kuchroo V. K., Glimcher L. H., T-bet represses TH 17 differentiation by preventing Runx1-mediated activation of the gene encoding ROR t Nature Immunology 2011 12 1 96 104
72. Veldhoen M., Hirota K., Westendorf A. M., Buer J., Dumoutier L., Renauld J. C., Stockinger B., The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins Nature 2008 453 7191 106 109 (Pubitemid 351630329)
73. Kimura A., Naka T., Nohara K., Fujii-Kuriyama Y., Kishimoto T., Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells Proceedings of the National Academy of Sciences of the United States of America 2008 105 28 9721 9726 (Pubitemid 352031367)
74. Schraml B. U., Hildner K., Ise W., Lee W. L., Smith W. A. E., Solomon B., Sahota G., Sim J., Mukasa R., Cemerski S., Hatton R. D., Stormo G. D., Weaver C. T., Russell J. H., Murphy T. L., Murphy K. M., The AP-1 transcription factor Batf controls T H 17 differentiation Nature 2009 460 7253 405 409
75. Brstle A., Heink S., Huber M., Rosenplnter C., Stadelmann C., Yu P., Arpaia E., Mak T. W., Kamradt T., Lohoff M., The development of inflammatory TH-17 cells requires interferon-regulatory factor 4 Nature Immunology 2007 8 9 958 966 (Pubitemid 47300010)
76. Chen Q., Yang W., Gupta S., Biswas P., Smith P., Bhagat G., Pernis A. B., IRF-4-binding protein inhibits interleukin-17 and interleukin-21 production by controlling the activity of IRF-4 transcription factor Immunity 2008 29 6 899 911
77. Korn T., Bettelli E., Gao W., Awasthi A., Jger A., Strom T. B., Oukka M., Kuchroo V. K., IL-21 initiates an alternative pathway to induce proinflammatory T (H)17 cells Nature 2007 448 7152 484 487 (Pubitemid 47123515)
78. Nurieva R., Yang X. O., Martinez G., Zhang Y., Panopoulos A. D., Ma L., Schluns K., Tian Q., Watowich S. S., Jetten A. M., Dong C., Essential autocrine regulation by IL-21 in the generation of inflammatory T cells Nature 2007 448 7152 480 483 (Pubitemid 47123514)
79. Langrish C. L., Chen Y., Blumenschein W. M., Mattson J., Basham B., Sedgwick J. D., McClanahan T., Kastelein R. A., Cua D. J., IL-23 drives a pathogenic T cell population that induces autoimmune inflammation Journal of Experimental Medicine 2005 201 2 233 240 (Pubitemid 40189432)
80. Zhou L., Ivanov I. I., Spolski R., Min R., Shenderov K., Egawa T., Levy D. E., Leonard W. J., Littman D. R., IL-6 programs TH-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways Nature Immunology 2007 8 9 967 974 (Pubitemid 47300011)
81. Ghoreschi K., Laurence A., Yang X. P., Tato C. M., McGeachy M. J., Konkel J. E., Ramos H. L., Wei L., Davidson T. S., Bouladoux N., Grainger J. R., Chen Q., Kanno Y., Watford W. T., Sun H. W., Eberl G., Shevach E. M., Belkaid Y., Cua D. J., Chen W., O'Shea J. J., Generation of pathogenic TH 17 cells in the absence of TGF- 2 signalling Nature 2010 467 7318 967 971
82. Chen W., Jin W., Hardegen N., Lei K. J., Li L., Marinos N., McGrady G., Wahl S. M., Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF- induction of transcription factor Foxp3 Journal of Experimental Medicine 2003 198 12 1875 1886 (Pubitemid 38032120)
83. Li M. O., Wan Y. Y., Flavell R. A., T Cell-Produced Transforming Growth Factor- 1 Controls T Cell Tolerance and Regulates Th1- and Th17-Cell Differentiation Immunity 2007 26 5 579 591 (Pubitemid 46756347)
84. Kriegel M. A., Li M. O., Sanjabi S., Wan Y. Y., Flavell R. A., Transforming growth factor- : recent advances on its role in immune tolerance Current Rheumatology Reports 2006 8 2 138 144 (Pubitemid 44623982)
85. Yoshimura A., Muto G., TGF- function in immune suppression Current Topics in Microbiology and Immunology 2011 350 127 147
86. Fontenot J. D., Gavin M. A., Rudensky A. Y., Foxp3 programs the development and function of CD4+CD25+ regulatory T cells Nature Immunology 2003 4 4 330 336 (Pubitemid 36432314)
87. Yagi H., Nomura T., Nakamura K., Yamazaki S., Kitawaki T., Hori S., Maeda M., Onodera M., Uchiyama T., Fujii S., Sakaguchi S., Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells International Immunology 2004 16 11 1643 1656
88. Takimoto T., Wakabayashi Y., Sekiya T., Inoue N., Smad2 and Smad3 are redundantly essential for the TGF- -mediated regulation of regulatory T plasticity and Th1 development Journal of Immunology 2010 185 2 842 855
89. Tone Y., Furuuchi K., Kojima Y., Tykocinski M. L., Greene M. I., Tone M., Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer Nature Immunology 2008 9 2 194 202
90. Martinez G. J., Zhang Z., Chung Y., Reynolds J. M., Lin X., Jetten A. M., Feng X. H., Dong C., Smad3 differentially regulates the induction of regulatory and inflammatory T cell differentiation Journal of Biological Chemistry 2009 284 51 35283 35286
91. Laurence A., Tato C. M., Davidson T. S., Kanno Y., Chen Z., Yao Z., Blank R., Meylan F., Siegel R., Hennighausen L., Shevach E. M., O'Shea J., Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation Immunity 2007 26 3 371 381 (Pubitemid 46413906)
92. Davidson T. S., DiPaolo R. J., Andersson J., Shevach E. M., Cutting edge: IL-2 is essential for TGF- -mediated induction of Foxp3+ T regulatory cells Journal of Immunology 2007 178 7 4022 4026 (Pubitemid 46492349)
93. Burchill M. A., Yang J., Vogtenhuber C., Blazar B. R., Farrar M. A., IL-2 receptor -dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells Journal of Immunology 2007 178 1 280 290 (Pubitemid 46033611)
94. Brandenburg S., Takahashi T., de la Rosa M., Janke M., Karsten G., Muzzulini T., Orinska Z., Bulfone-Paus S., Scheffold A., IL-2 induces in vivo suppression by CD4 + CD25 + Foxp3 + regulatory T cells European Journal of Immunology 2008 38 6 1643 1653
95. Kaplan M. H., Glosson N. L., Stritesky G. L., Yeh N., Kinzfogl J., Rohrabaugh S. L., Goswami R., Pham D., Levy D. E., Brutkiewicz R. R., Blum J. S., Cooper S., Hangoc G., Broxmeyer H. E., STAT3-dependent IL-21 production from T helper cells regulates hematopoietic progenitor cell homeostasis Blood 2011 117 23 6198 6201
96. Wu Y., Borde M., Heissmeyer V., Feuerer M., Lapan A. D., Stroud J. C., Bates D. L., Guo L., Han A., Ziegler S. F., Mathis D., Benoist C., Chen L., Rao A., FOXP3 controls regulatory T cell function through cooperation with NFAT Cell 2006 126 2 375 387 (Pubitemid 44092960)
97. Awasthi A., Carrier Y., Peron J. P. S., Bettelli E., Kamanaka M., Flavell R. A., Kuchroo V. K., Oukka M., Weiner H. L., A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells Nature Immunology 2007 8 12 1380 1389 (Pubitemid 350131175)
98. Gregori S., Tomasoni D., Pacciani V., Scirpoli M., Battaglia M., Magnani C. F., Hauben E., Roncarolo M. G., Differentiation of type 1 T regulatory cells (Tr1) by tolerogenic DC-10 requires the IL-10-dependent ILT4/HLA-G pathway Blood 2010 116 6 935 944
99. Pot C., Jin H., Awasthi A., Liu S. M., Lai C. Y., Madan R., Sharpe A. H., Karp C. L., Miaw S. C., Ho I. C., Kuchroo V. K., Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells Journal of Immunology 2009 183 2 797 801
100. Apetoh L., Quintana F. J., Pot C., Joller N., Xiao S., Kumar D., Burns E. J., Sherr D. H., Weiner H. L., Kuchroo V. K., The Aryl hydrocarbon Receptor (AhR) interacts with c-Maf to promote the differentiation of IL-27-induced regulatory type 1 (T R 1) cells Nature Immunology 2010 11 9 854 861
101. Vinuesa C. G., Tangye S. G., Moser B., Mackay C. R., Follicular B helper T cells in antibody responses and autoimmunity Nature Reviews Immunology 2005 5 11 853 865 (Pubitemid 41581667)
102. Breitfeld D., Ohl L., Kremmer E., Ellwart J., Sallusto F., Lipp M., Frster R., Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production Journal of Experimental Medicine 2000 192 11 1545 1551
103. Vogelzang A., McGuire H. M., Yu D., Sprent J., Mackay C. R., King C., A fundamental role for interleukin-21 in the generation of T follicular helper cells Immunity 2008 29 1 127 137
104. Nurieva R. I., Chung Y., Hwang D., Yang X. O., Kang H. S., Ma L., Wang Y. H., Watowich S. S., Jetten A. M., Tian Q., Dong C., Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages Immunity 2008 29 1 138 149
105. Halonen S. K., Taylor G. A., Weiss L. M., Gamma interferon-induced inhibition of Toxoplasma gondii in astrocytes is mediated by IGTP Infection and Immunity 2001 69 9 5573 5576 (Pubitemid 32786493)
106. Akiba H., Takeda K., Kojima Y., Usui Y., Harada N., Yamazaki T., Ma J., Tezuka K., Yagita H., Okumura K., The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo Journal of Immunology 2005 175 4 2340 2348 (Pubitemid 41113843)
107. Bossaller L., Burger J., Draeger R., Grimbacher B., Knoth R., Plebani A., Durandy A., Baumann U., Schlesier M., Welcher A. A., Peter H. H., Warnatz K., ICOS deficiency is associated with a severe reduction of CXCR5 +CD4 germinal center Th Cells Journal of Immunology 2006 177 7 4927 4932 (Pubitemid 44469829)
108. Nurieva R. I., Chung Y., Martinez G. J., Yang X. O., Tanaka S., Matskevitch T. D., Wang Y. H., Dong C., Bcl6 mediates the development of T follicular helper cells Science 2009 325 5943 1001 1005
109. Bending D., De La Pea H., Veldhoen M., Phillips J. M., Uyttenhove C., Stockinger B., Cooke A., Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice Journal of Clinical Investigation 2009 119 3 565 572
110. Lee Y. K., Turner H., Maynard C. L., Oliver J. R., Chen D., Elson C. O., Weaver C. T., Late developmental plasticity in the T helper 17 lineage Immunity 2009 30 1 92 107
111. Xu L., Kitani A., Fuss I., Strober W., Cutting edge: regulatory T cells induce CD4+CD25 -Foxp3- T cells or are self-induced to become Th17 cells in the absence of exogenous TGF- Journal of Immunology 2007 178 11 6725 6729 (Pubitemid 46847395)
112. Tsuji M., Komatsu N., Kawamoto S., Suzuki K., Kanagawa O., Honjo T., Hori S., Fagarasan S., Preferential generation of follicular B helper T cells from Foxp3 + T cells in gut Peyer's patches Science 2009 323 5920 1488 1492
113. Zheng Y., Chaudhry A., Kas A., de Roos P., Kim J. M., Chu T. T., Corcoran L., Treuting P., Klein U., Rudensky A. Y., Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control T H 2 responses Nature 2009 458 7236 351 356
114. del Prete G., Human Th1 and Th2 lymphocytes: their role in the pathophysiology of atopy Allergy 1992 47 5 450 455
115. Murray H. W., Rubin B. Y., Carriero S. M., Human mononuclear phagocyte antiprotozoal mechanisms: Oxygen-dependent vs oxygen-independent activity against intracellular Toxoplasma gondii Journal of Immunology 1985 134 3 1982 1988 (Pubitemid 15128972)
116. Boehm U., Klamp T., Groot M., Howard J. C., Cellular responses to interferon- Annual Review of Immunology 1997 15 749 795
117. Melzer T., Duffy A., Weiss L. M., Halonen S. K., The gamma interferon (IFN- )-inducible GTP-binding protein IGTP is necessary for Toxoplasma vacuolar disruption and induces parasite egression in IFN- -stimulated astrocytes Infection and Immunity 2008 76 11 4883 4894
118. Taylor G. A., Feng C. G., Sher A., p47 GTPases: regulators of immunity to intracellular pathogens Nature Reviews Immunology 2004 4 2 100 109 (Pubitemid 38209204)
119. Chiang E. Y., Kolumam G. A., Yu X., Francesco M., Ivelja S., Peng I., Gribling P., Shu J., Lee W. P., Refino C. J., Balazs M., Paler-Martinez A., Nguyen A., Young J., Barck K. H., Carano R. A. D., Ferrando R., Diehl L., Chatterjea D., Grogan J. L., Targeted depletion of lymphotoxin- -expressing T H 1 and T H 17 cells inhibits autoimmune disease Nature Medicine 2009 15 7 766 773
120. Suen W. E., Bergman C. M., Hjelmstrm P., Ruddle N. H., A critical role for lymphotoxin in experimental allergic encephalomyelitis Journal of Experimental Medicine 1997 186 8 1233 1240 (Pubitemid 27469018)
121. Kim H. P., Imbert J., Leonard W. J., Both integrated and differential regulation of components of the IL-2/IL-2 receptor system Cytokine and Growth Factor Reviews 2006 17 5 349 366 (Pubitemid 44604346)
122. Gattinoni L., Klebanoff C. A., Palmer D. C., Wrzesinski C., Kerstann K., Yu Z., Finkelstein S. E., Theoret M. R., Rosenberg S. A., Restifo N. P., Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8 + T cells Journal of Clinical Investigation 2005 115 6 1616 1626 (Pubitemid 40814670)
123. Williams M. A., Tyznik A. J., Bevan M. J., Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cells Nature 2006 441 7095 890 893
124. Wuest T. Y., Willette-Brown J., Durum S. K., Hurwitz A. A., The influence of IL-2 family cytokines on activation and function of naturally occurring regulatory T cells Journal of Leukocyte Biology 2008 84 4 973 980
125. Sokol C. L., Chu N. Q., Yu S., Nish S. A., Laufer T. M., Medzhitov R., Basophils function as antigen-presenting cells for an allergen-induced T helper type 2 response Nature Immunology 2009 10 7 713 720
126. Steinke J. W., Borish L., Th2 cytokines and asthma. Interleukin-4: its role in the pathogenesis of asthma, and targeting it for asthma treatment with interleukin-4 receptor antagonists Respiratory Research 2001 2 2 66 70 (Pubitemid 34187909)
127. Doucet C., Brouty-Boyé D., Pottin-Clemenceau C., Jasmin C., Canonica G. W., Azzarone B., IL-4 and IL-13 specifically increase adhesion molecule and inflammatory cytokine expression in human lung fibroblasts International Immunology 1998 10 10 1421 1433 (Pubitemid 28451436)
128. Martinez-Moczygemba M., Huston D. P., Biology of common receptor-signaling cytokines: IL-3, IL-5, and GM-CSF Journal of Allergy and Clinical Immunology 2003 112 4 653 665
129. Little F. F., Cruikshank W. W., Center D. M., IL-9 stimulates release of chemotactic factors from human bronchial epithelial cells American Journal of Respiratory Cell and Molecular Biology 2001 25 3 347 352 (Pubitemid 32918917)
130. Wynn T. A., IL-13 effector functions Annual Review of Immunology 2003 21 425 456 (Pubitemid 37174537)
131. Couper K. N., Blount D. G., Riley E. M., IL-10: the master regulator of immunity to infection Journal of Immunology 2008 180 9 5771 5777
132. Fort M. M., Cheung J., Yen D., Li J., Zurawski S. M., Lo S., Menon S., Clifford T., Hunte B., Lesley R., Muchamuel T., Hurst S. D., Zurawski G., Leach M. W., Gorman D. M., Rennick D. M., IL-25 Induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo Immunity 2001 15 6 985 995 (Pubitemid 34075378)
133. Kleinschek M. A., Owyang A. M., Joyce-Shaikh B., Langrish C. L., Chen Y., Gorman D. M., Blumenschein W. M., McClanahan T., Brombacher F., Hurst S. D., Kastelein R. A., Cua D. J., IL-25 regulates Th17 function in autoimmune inflammation Journal of Experimental Medicine 2007 204 1 161 170 (Pubitemid 46148766)
134. Ballantyne S. J., Barlow J. L., Jolin H. E., Nath P., Williams A. S., Chung K. F., Sturton G., Wong S. H., McKenzie A. N. J., Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma Journal of Allergy and Clinical Immunology 2007 120 6 1324 1331 (Pubitemid 350216590)
135. Zaiss D. M., Yang L., Shah P. R., Kobie J. J., Urban J. F., Mosmann T. R., Amphiregulin, a TH2 cytokine enhancing resistance to nematodes Science 2006 314 5806 1746 (Pubitemid 44969079)
136. Xing J., Wu Y., Ni B., Th9: a new player in asthma pathogenesis? Journal of Asthma 2011 48 2 115 125
137. Annunziato F., Cosmi L., Santarlasci V., Maggi L., Liotta F., Mazzinghi B., Parente E., Fil L., Ferri S., Frosali F., Giudici F., Romagnani P., Parronchi P., Tonelli F., Maggi E., Romagnani S., Phenotypic and functional features of human Th17 cells Journal of Experimental Medicine 2007 204 8 1849 1861 (Pubitemid 47240944)
138. Weaver C. T., Harrington L. E., Mangan P. R., Gavrieli M., Murphy K. M., Th17: an effector CD4 T cell lineage with regulatory T Cell ties Immunity 2006 24 6 677 688 (Pubitemid 43867371)
139. Ivanov I. I., McKenzie B. S., Zhou L., Tadokoro C. E., Lepelley A., Lafaille J. J., Cua D. J., Littman D. R., The Orphan Nuclear Receptor ROR t Directs the Differentiation Program of Proinflammatory IL-17 + T Helper Cells Cell 2006 126 6 1121 1133 (Pubitemid 44380299)
140. Gaffen S. L., Structure and signalling in the IL-17 receptor family Nature Reviews Immunology 2009 9 8 556 567
141. Moseley T. A., Haudenschild D. R., Rose L., Reddi A. H., Interleukin-17 family and IL-17 receptors Cytokine and Growth Factor Reviews 2003 14 2 155 174 (Pubitemid 36389528)
142. Korn T., Bettelli E., Gao W., Awasthi A., Jger A., Strom T. B., Oukka M., Kuchroo V. K., IL-21 initiates an alternative pathway to induce proinflammatory T H17 cells Nature 2007 448 7152 484 487 (Pubitemid 47123515)
143. Leonard W. J., Spolski R., Interleukin-21: a modulator of lymphoid proliferation, apoptosis and differentiation Nature Reviews Immunology 2005 5 9 688 698 (Pubitemid 43086171)
144. Aujla S. J., Chan Y. R., Zheng M., Fei M., Askew D. J., Pociask D. A., Reinhart T. A., McAllister F., Edeal J., Gaus K., Husain S., Kreindler J. L., Dubin P. J., Pilewski J. M., Myerburg M. M., Mason C. A., Iwakura Y., Kolls J. K., IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia Nature Medicine 2008 14 3 275 281 (Pubitemid 351347908)
145. Zenewicz L. A., Yancopoulos G. D., Valenzuela D. M., Murphy A. J., Karow M., Flavell R. A., Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation Immunity 2007 27 4 647 659 (Pubitemid 47615503)
146. Sakaguchi S., Ono M., Setoguchi R., Yagi H., Hori S., Fehervari Z., Shimizu J., Takahashi T., Nomura T., Foxp3+CD25+CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease Immunological Reviews 2006 212 8 27 (Pubitemid 44116697)
147. Ouyang W., Rutz S., Crellin N. K., Valdez P. A., Hymowitz S. G., Regulation and functions of the IL-10 family of cytokines in inflammation and disease Annual Review of Immunology 2011 29 71 109
148. Asseman C., Mauze S., Leach M. W., Coffman R. L., Powrie F., An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation Journal of Experimental Medicine 1999 190 7 995 1004
149. Jutel M., Akdis C., T-cell regulatory mechanisms in specific immunotherapy Chemical Immunology and Allergy 2008 94 158 177
150. Li M. O., Wan Y. Y., Flavell R. A., T Cell-Produced Transforming Growth Factor- 1 Controls T Cell Tolerance and Regulates Th1- and Th17-Cell Differentiation Immunity 2007 26 5 579 591 (Pubitemid 46756347)
151. Fazilleau N., Mark L., McHeyzer-Williams L. J., McHeyzer-Williams M. G., Follicular helper T Cells: lineage and location Immunity 2009 30 3 324 335